非传统生物标志物对慢性肾脏病合并心血管疾病风险预测的意义

改善心血管疾病的管理有可能显著改善慢性肾脏病患者的健康和结局.目前已发现心肌肌钙蛋白、B型利钠肽、冠脉钙化与慢性肾脏病患者心血管疾病死亡风险相关,并且有助于心血管疾病风险预测.本文主要总结非传统生物标志物升高对慢性肾脏病合并心血管疾病风险预测的意义.     

慢性肾脏病血管钙化与矿物质代谢的相互作用——老问题新观点北大核心CSCD

血管钙化是慢性肾脏病心血管并发症的主要原因。慢性肾脏病患者血管钙化的加重是多个相互关联的机制所致,如矿物质代谢的异常、抗矿化系统的失调等。目前认为血管钙化是一个多因素的主动过程。过去几年来血管钙化的触发因素和复杂的分子机制出现了新观点,研究发现钙磷稳态的失调、钙磷酸盐矿物质的生成和生长、降磷措施的应用,均与血管钙化的发生和加重关系密切。文章重点讨论了矿物质代谢在慢性肾脏病血管钙化的发生发展以及治疗中的作用。     

慢性肾脏病患者心血管系统钙化的病理生理机制

正心血管系统钙化包括血管内膜钙化、血管中膜钙化及心脏瓣膜钙化3种病理类型,被认为是心血管事件发病率和死亡率强有力的预测因素。慢性肾脏病(chronic kidney disease,CKD)尤其是糖尿病肾病,会加速血管、心脏瓣膜和心肌钙化以及出现尿路血管钙化病变的罕见病症。钙化发生、发展的主要病理生理机制是促进剂(钙和磷酸盐)与抑制剂(如胎球蛋白A和基质γ羧基谷氨酸蛋白)不平衡[1]。除生     

糖尿病肾病患者心血管钙化的发生率及特点

目的:观察糖尿病肾病患者心血管钙化的发生情况,并分析其影响因素。方法:选取慢性肾脏病(CKD)2~5期非透析糖尿病肾病患者270例(2期40例、3期121例、4期63例、5期46例),完善心血管钙化的相关实验室检查,选用螺旋CT评分冠状动脉钙化,腹部侧位平片评分腹主动脉钙化,心脏彩超观察心脏瓣膜钙化情况,并采用Logistic回归分析心血管钙化的相关危险因素。结果:CKD 2~5期患者血磷逐渐升高,血钙逐渐降低,全段甲状旁腺激素逐渐升高,25羟维生素D逐渐下降(P0.01)。所有患者心血管钙化发生率为70.3%,其中冠状动脉钙化、腹主动脉钙化和瓣膜钙化发生率分别为55.1%、43.4%和23.9%。CKD 2~5期心血管钙化的总发生率分别为72.5%、73.6%、66.7%和63.0%。心血管钙化与年龄、糖尿病病程、高血压病程、心血管疾病史、颈部血管粥样斑块等相关,而与性别、血脂异常、血钙、血磷、全段甲状旁腺激素及CKD分期无关。其中年龄、心脑血管疾病史和颈部血管粥样斑块是冠状动脉和腹主动脉钙化的独立危险因素,年龄是心脏瓣膜钙化的独立危险因素。结论:糖尿病肾病患者心血管钙化发生率高,在CKD 2期钙磷代谢紊乱不明显时即已出现明显钙化。心血管钙化发生率与传统心血管疾病危险因素相关,而与钙磷代谢指标及CKD分期无显著相关。     

慢性肾脏病钙磷代谢紊乱及骨病的处理

慢性肾脏病矿物质及骨代谢紊乱是慢性肾脏病患者最常见的慢性并发症之一,长期的骨及钙磷代谢异常不仅会引起骨痛、骨骼畸形,还会导致血管及心瓣膜钙化,心血管事件高发。治疗的重点是降低高血磷和维持血钙,控制甲状旁腺激素在目标范围。     

慢性肾脏病合理应用活性维生素D及专家共识

慢性肾脏病(CKD)患者普遍存在矿物质和骨代谢紊乱,2005年KDIGO将其定义为:慢性肾脏病相关性矿物质及骨代谢紊乱( CKD - MBD),可表现为钙、磷、甲状旁腺激素(PTH)或维生素D代谢异常,骨转化、矿化、骨容量、骨骼线性生长或骨强度的异常,还可表现为血管或其他软组织钙化.有研究显示,慢性肾脏病患者早期即出现维生素D的减少及矿物质和骨代谢紊乱,并贯穿于肾功能进行性减退的全过程[1,2],常与因血管钙化导致心血管结构和功能的损害有关,并和患者的死亡率和疾病的发生率上升相关[3-5].合理应用活性维生素D不仅可以治疗慢性肾脏病患者出现的矿物质及骨代谢紊乱,还可以降低蛋白尿,减少炎症,降低血压,延缓终末期肾病的进展,提高慢性肾脏病患者的生存质量,降低死亡率[6-9].     

胎球蛋白A对腹膜透析患者冠状动脉钙化发生起始的影响因素分析

心血管疾病(cardiovascular disease,CVD)是慢性肾脏病(chronic kidney disease,CKD)患者的主要死亡原因.终末期肾病(end-stage renal disease,ESRD)患者由于心血管事件造成的死亡占总死亡原因的50％以上[1].而血管钙化与心血管事件的发生密切相关...     

关于慢性肾脏病心血管钙化诊治研究的进展

慢性肾脏病(CKD)患者易发生心血管相关并发症,其中心血管钙化是导致心血管疾病发生及死亡的重要危险因素。最近有研究表明可通过使用双磷酸盐,补充维生素K、镁等方法来治疗心血管钙化。本综述就最新的研究结果进行了简述,并评估了这些新的治疗策略对CKD患者心血管钙化的可能影响。     

慢性肾脏病动脉中层钙化细胞生物学机制研究进展

<正>慢性肾脏病(CKD)是公认的"全球公共健康问题",我国成人CKD的患病率已达10.8%[1]。随着肾功能进行性恶化,心血管疾病(CVD)成为CKD患者的主要死亡原因之一,而血管钙化是其中最常见的病理表现,血管钙化导致的死亡率约占终末期肾脏病(ESRD)总病死率的30%左右[2]。动脉中层钙化是慢性肾脏病患者血管钙化的主要类型,血管平滑肌细胞(VSMCs)是动脉中层的主要成分,慢性肾脏病的多种危险因素如高磷、高钙、炎症等可诱导     

慢性肾脏病动态血压监测的研究进展

高血压与左室肥厚有关,可加速慢性肾脏疾病、移植肾、脑萎缩的进展,增加心血管事件发生率,是心血管和肾脏病的主要风险因子。收缩压（SBP）与脉压呈明显相关,24h脉压增加是心血管事件的预测因子。研究显示,动态血压监测（ABPM）在预测慢性肾病患者左心室肥大和肾功能不全进展方面比诊室血压好。在终末期肾病中,ABPM在预测血液透析患者病死率方面优于诊室血压。现结合文献,对慢性肾脏病ABPM检测的研究进展作一综述。     

Vascular calcification in patients with chronic kidney disease

Chronic kidney disease (CKD) represents an extremely common condition, and cardiovascular diseases are frequently reported in this patient population. Traditional risk factors are not accurate prognostic predictors in CKD patients, and new potential markers to predict the cardiovascular involvement in uremic patients need to be identified. Vascular calcification (VC) represents a hallmark of the atherosclerotic process in CKD. This review summarizes the processes responsible for VC (particularly focusing on the mechanisms operative in the presence of renal dysfunction), discusses the utility of computer tomography modalities in the detection of VC in patients with CKD, and reports the potential role of VC as pathophysiological link between kidney disease and cardiovascular events.     

慢性肾脏病血管钙化机制的研究进展

慢性肾脏病（chronic kidney disease, CKD）是世界公认的健康问题,我国CKD的患病率约为10.8%,并且CKD的死亡率也很高。心血管疾病（cardiovascular disease, CVD）是CKD最常见的死亡原因,而血管钙化（vascular calcification, VC)是导致CVD的重要危险因素。因此本文对CKD血管钙化的流行病学现状、病理学特点、危险因素、发病机制等方面进行综述,希望能为血管钙化的防治提供新的思路。     

Vitamin D receptor activation and prevention of arterial ageing

In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.     

Reprint of: Vitamin D receptor activation and prevention of arterial ageing

In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.     

血管钙化的分子机理与临床展望

Cardiovascular disease is a major consideration in the patients with diabetes and chronic kidney disease （CKD）. Vascular calcification is an important problem among these patients, and contributes to the increased risk of cardiovascular events by a variety of mechanism, including an increase in arterial stiffness by medial calcification or an increase in plaque vul- nerability by a specific type of atherosclerotic calcification.     

TAM受体酪氨酸激酶与肾脏疾病

TAM(TYRO3、AXL、MER)受体酪氨酸激酶(TAM-RTKs)属广泛表达的受体酪氨酸激酶亚家族,在细胞增殖、生存、迁移、胞葬、炎症及免疫调控、血小板稳定等多方面发挥重要功能。动物模型研究发现,肾脏局部或全身的TAM-RTKs功能异常广泛参与Thy1肾小球肾炎、糖尿病肾病、抗肾小球基膜肾炎、单侧输尿管梗阻、肾毒性血清肾炎、急性肾损伤、高血压肾损伤等肾脏疾病的发病机制中。此外,肾脏TAM-RTKs及循环中分泌型TAM-RTKs的水平同狼疮性肾炎、糖尿病肾病、慢性肾脏病等疾病严重程度存在关联,有望成为新型疾病分子标志物。TAM-RTKs亦参与慢性肾脏病相关血管粥样硬化及钙化的过程中。本文将对TAM-RTKs在肾脏疾病中的研究进展进行综述。     

Vascular calcification in patients with chronic kidney disease

Vascular calcification is very prevalent in patients with chronic kidney disease (CKD). In addition to having more traditional cardiovascular (CV) risk factors, CKD patients also have a number of non-traditional CV risk factors that may play a prominent role in the pathogenesis of vascular calcification. The transformation of vascular smooth muscle cells into osteoblast-like cells seems to be a key element in the pathogenesis of vascular calcification in the presence of calcium (Ca) and phosphorus (P) deposition due to abnormal bone metabolism and impaired renal excretion. Vascular calcification causes increased arterial stiffness, left ventricular hypertrophy, decreased coronary artery perfusion, myocardial ischemia, and increased cardiovascular morbidity and mortality. Although current treatment strategies focus on correcting abnormal Ca, P, parathyroid hormone, or vitamin D levels in CKD, a better understanding of the mechanisms of abnormal tissue calcification may lead to the development of new therapeutic agents that are capable of reducing vascular calcification and improving the CV outcome of CKD patients. This review article summarizes the following: (i) the pathophysiological mechanism responsible for vascular calcification; (ii) the methods of detecting vascular calcification in CKD patients; and (iii) the treatment of vascular calcification in CKD patients.     

Bone morphogenetic proteins in vascular calcification

Vascular calcification is a common problem among the elderly and those with chronic kidney disease (CKD) and diabetes. The process of tunica media vascular calcification in CKD appears to involve a phenotypic change in the vascular smooth muscle cell (VSMC) resulting in cell-mediated mineralization of the extracellular matrix. The bone morphogenetic proteins (BMPs) are important regulators in orthotopic bone formation, and their localization at sites of vascular calcification raises the question of their role. In this review, we will discuss the actions of the BMPs in vascular calcification. Although the role of BMP-2 in vascular calcification is not proven, it has been the most studied member of the BMP family in this disease process. The role of BMP-2 may be through inducing osteoblastic differentiation of VSMCs through induction of MSX-2, or by inducing apoptosis of VSMCs, a process thought critical in the initiation of vascular calcification. Additionally, BMP-2 may be related to loss of regulation of the matrix Gla protein. A second BMP, BMP-7, less studied than BMP-2 may have opposing actions in vascular calcification. In postnatal life, BMP-7 is expressed primarily in the kidney, and expression is diminished by renal injury. BMP-7 is an important regulator of skeletal remodeling and the VSMC phenotype. BMP-7 restores skeletal anabolic balance in animal models of CKD with disordered skeletal modeling, also reducing serum phosphate in the process. BMP-7 also reverses vascular calcification in CKD, and reduction in vascular calcification is due, in part, to reduced serum phosphate, an important inducer of VSMC-mediated vascular mineralization and in part to direct actions on the VSMC.     

Inflammation and vascular calcification

Both vascular calcification and inflammation are common in patients with chronic kidney disease (CKD). In patients on dialysis, there is increased coronary artery and peripheral artery calcification compared to the general population. Both intimal (atherosclerotic) and medial calcification in CKD patients are associated with increased morbidity and mortality. Vascular calcification is an active cell-mediated process, and likely reflects a transformation of vascular smooth muscle cells to osteoblast-like cells. Pooled uremic serum can induce this transformation, but the mechanism by which it does so is not yet clear. Several mediators of inflammation such as oxidation, carbonyl stress, C-reactive protein, and cytokines may directly stimulate vascular calcification. In addition, inflammation itself reduces fetuin-A, a naturally occurring inhibitor of vascular calcification which binds excess mineral in serum. The combination of the acceleration of vascular calcification together with impaired defense mechanisms creates a uremic milieu primed for extra-osseous calcification.