替米沙坦对3期慢性肾脏病患者内皮功能及氧化应激的影响

<正>慢性肾脏病(CKD)在全球范围的发病率呈稳步增高趋势,根据流行病学研究显示,我国普通人群中CKD的患病率约为9%～13%[1]。若未能对CKD进行有效治疗,它们最终都将进入终末期肾脏病(ESRD)。ESRD患者的病死率为9%,是一般人群的10～20倍。动脉粥样硬化是慢性肾功能衰竭患者常见的并发症,也是ESRD长期透析患者主要的致死原因之一。近年研究表明,慢性肾功能不全患者血浆血管内皮功能的     

脉搏波传导速度与肾小球滤过率评估值的相关性研究

目的探讨非透析慢性肾脏病(chronic kidney disease,CKD)患者的脉搏波传导速度(pulse wave veloci-ty,PWV)与动脉粥样硬化程度的关系。方法选择诊断明确的非透析CKD住院患者118例,通过简化MDRD公式计算肾小球滤过率评估值(evaluate glomerular filtration rate,eGFR),按eGFR水平分为CKD 1期组、CKD 2期组、CKD 3期组、CKD 4期组、CKD 5期组测定PWV值,采用SPSS 11.5软件包进行统计学处理。结果 PWV值在各组间的差异有统计学意义(P<0.01);Logistic逐步回归分析显示,年龄(P<0.01),eGFR(P<0.01)为PWV值主要影响因素。结论 eG-FR是动脉粥样硬化的独立危险因素,肾功能减退与动脉粥样硬化程度密切相关,PWV是评估CKD患者动脉粥样硬化程度的重要临床指标。     

Study on correlation between eGFR and PWV

目的 探讨非透析慢性肾脏病(chronic kidney disease,CKD)患者的脉搏波传导速度(pulse wave velocity,PWV)与动脉粥样硬化程度的关系.方法 选择诊断明确的非透析CKD住院患者118例,通过简化MDRD公式计算肾小球滤过率评估值(evaluate glomerular filtration rate,eGFR),按eGFR水平分为CKD 1期组、CKD 2期组、CKD 3期组、CKD 4期组、CKD 5期组测定PWV值,采用SPSS 11.5软件包进行统计学处理.结果 PWV值在各组间的差异有统计学意义(P＜0.01);Logistic逐步回归分析显示,年龄(P＜0.01),eGFR(P＜0.01)为PWV值主要影响因素.结论 eGFR是动脉粥样硬化的独立危险因素,肾功能减退与动脉粥样硬化程度密切相关,PWV是评估CKD患者动脉粥样硬化程度的重要临床指标.     

高位结肠透析净化排毒法治疗终末期肾衰竭的创新研究

目的 探讨高位结肠透析净化排毒法治疗终末期肾衰竭(end-stage renal disease,ESRD),即慢性肾脏病5期(chronic kidney disease,CKD5)的疗效.方法 选择暂时无条件或拒绝接受透析和肾移植的CKD5期患者4例,在常规CKD治疗的基础上,用JS-308型结肠透析机进行高位结肠透析净化排毒法治疗,观察治疗效果.结果 3例行结肠透析净化排毒治疗的分别延缓了21个月、19个月、6个月进入血液透析或腹膜透析阶段.1例已经应用高位结肠透析净化排毒法治疗6年4个月,目前仍在应用本疗法,各项指标基本稳定,营养状态及生活质量良好.结论 高位结肠透析净化排毒法是治疗ESRD最有效的弥补办法,不仅能延缓进入肾替代治疗的时间,而且可延长生存时间.     

非透析慢性肾脏病患者脉搏波传导速度与尿蛋白量的相关性研究

目的通过测量非透析慢性肾脏病(CKD)(1~5期)患者的脉搏波传导速度(PWV)及24 h尿蛋白定量,分析PWV和24 h尿蛋白定量的关系。方法横断面研究住院患者118例,均为诊断明确的非透析CKD患者,按照尿蛋白定量水平(<1.0 g/24 h;1.0~3.5 g/24 h;≥3.5 g/24 h)分为三组:A组40例,B组40例,C组38例;健康体检者58例为健康对照组。记录患者性别、年龄、身高、体重、吸烟状况、血压、空腹血糖、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、肾功能。通过简化的肾脏病膳食改良公式计算肾小球滤过率估计值(e GFR),测定PWV值及24 h尿蛋白定量。结果与健康对照组比较,A、B、C组患者PWV值明显增高,差异具有统计学意义(P<0.01);与A组比较,B、C组患者的PWV值明显增高,差异具有统计学意义(P<0.01);与B组比较,C组患者PWV值明显增高,差异具有统计学意义(P<0.01);Spearman相关分析显示,年龄、糖尿病、高血压、HDL-C、LDL-C、e GFR和尿蛋白定量为PWV的独立危险因素,差异具有统计学意义(P<0.05)。结论影响非透析慢性肾脏病患者的脉搏波传导速度的因素有年龄、糖尿病、高血压、e GFR和尿蛋白定量,降低尿蛋白会改善患者的脉搏波传导速度。     

210例老年肾功能衰竭血液透析观察分析

随着人群平均寿命的延长，世界人口正在趋向老年化。因老年人群终末期肾脏病（ESRD）发病率的增长比其他任何人群都快，同时接受血液透析的老年人的比例在全球也呈快速增长趋势。但老龄人群存在着与年龄相关的脏器组织学、功能及代谢的特殊性，从而增加了透析治疗的困难，老年患者ESRD的治疗越来越受到临床医生的关注。血液透析和腹膜透析是目前终末期肾病的主要替代治疗方式，对于老年ESRD患者原则上这两种方式均可考虑。老年ESRD患者选择透析方式，要考虑年龄带来的生理变化，同样也要考虑到不同透析方式给这一特殊人群所带来的一系列影响。根据患者的实际情况进行个体化透析是十分关键的。     

腹膜透析相关性腹膜炎84例临床分析

据统计,目前终末期肾病(end stage renal disease,ESRD)患者每年以10%以上的速度增长,肾脏替代的三种选择中(包括肾移植、血液透析和腹膜透析),由于肾源的限制,故透析疗法成了目前ESRD的主要治疗方法。血液透析由于透析费用及需专业医务人操作的限制,故在肾脏病一体化治疗中,腹膜透析作为ESRD首选治疗已成为共识。自1976年首次开展腹膜透析以来,随着连接系统、消     

维持性血液透析对终末期肾病患者治疗转归及生存率的影响

目的评价分析维持性血液透析对终末期肾病患者(ESRD)治疗转归及生存率的影响。方法回顾性分析我院近5年来收治的110例ESRD患者临床资料,并分析本组患者治疗转归情况和生存率情况以及影响因素。结果 110例患者1年生存率为89.1%;3年生存率为78.2%;5年生存率为60.9%,随着透析时间的延长生存率呈现下降趋势;仍接受透析者有41.4%,改为腹膜透析者2.7%,肾移植7.7%,转其他医院者9.1%,死亡43例(占39.1%)。Cox回归多因素分析发现,患者首次透析年龄越小、透析次数越多,首次透析营养状况以及残余肾功能越多,则患者生存率越高,病死率越低。其中死亡因素为心脑血管事件32例,感染7例,消化道出血有3例,高钾血症2例。结论患者首次透析年龄、透析次数、首次透析营养状况以及开始透析残余肾功能等是ESRD患者维持性血液透析生存率的重要因素,临床应给予重视,以提高ESRD患者生存率。     

低蛋白饮食在慢性肾脏病患者中的应用

慢性肾病(chronic kidney disease,CKD)患者的一体化治疗中,饮食干预不容忽视。本文对低蛋白饮食在CKD4-5期患者中的应用进行系统回顾,侧重分析了低蛋白饮食在透析患者中应用的最新研究,发现降低饮食蛋白摄入量(dietary protein intake,DPI)对保护患者残肾功能、改善患者预后有益,有助于降低尿蛋白、减轻患者尿毒症症状,如高磷血症、血脂异常、高血压、代谢性酸中毒等。目前的研究表明低蛋白饮食在透析人群中应用是安全的。该研究领域尚需更多大规模前瞻性研究。     

慢性非透析肾脏病患者磷代谢与心血管疾病关系

据统计,目前我国慢性肾脏疾病(CKD)患者达10.8%,即约有1亿人群受到慢性肾脏疾病困扰,因此,慢性肾脏疾病是我国公共健康的难题[1].调查研究[2]表明,CKD患者由于心血管事件引起的死亡占总死亡原因半数以上.CKD人群除了具有导致心血管疾病的传统因素,如高血压、高血脂、糖尿病和尿毒症以外,CKD特有的危险因素,如血磷及磷相关调节激素-成纤维细胞生长因子23(FGF23)都是CKD患者心血管病死亡的独立危险因素.有研究[3]表明,在非透析人群中,排除年龄、性别、肾功能及血钙水平等相关因素干扰后,血磷每升高1mg/dL,全因死亡率增加23%,急性心肌梗死的风险增加35%,另一研究[4]也证实,当血磷每升高1mg/dL,全因死亡率增加26%,心血管事件的死亡率增加50%.本文对慢性肾脏病患者磷代谢异常及磷相关激素FGF23对非透析患者心血管系统的影响进行综述.     

Effect of Antihypertensive Agents on Arterial Stiffness as Evaluated by Pulse Wave Velocity

Structural and functional properties of the arterial wall have been reported to be altered in hypertension, even at early stages of the disease. Morbidity and mortality associated with hypertension are primarily related to arterial damage that may affect one or several organs. Considering the potential implications of arterial assessment in the prevention of cardiovascular disease, evaluation of the arterial effects of antihypertensive agents is recommanded by numerous authorities. Among the noninvasive and simple methods to evaluate large arteries, pulse wave velocity (PWV) measurement is widely used as an index of regional arterial stiffness. This method is related to the arterial geometry and wall function, simple and reproducible, and thus, can easily be applied in clinical trials. Several studies performed in various populations showed significant powerful interactions between PWV and cardiovascular risk factors. In addition, aortic PWV was shown to be a forceful marker and predictor of cardiovascular risk in normotensive individuals and patients with hypertension. Furthermore, aortic PWV was shown to be an independent predictor of all-cause mortality in patients with essential hypertension. In comparison with placebo, clinical studies have shown that in short and long term trials, antihypertensive agents improved arterial stiffness (as evidenced by a reduction in PWV) independently of blood pressure reduction. The decrease of PWV was more pronounced with long term treatment than with short term treatment. Whether antihypertensive agents differ in their arterial effects independently of blood pressure changes remains unclear. Pharmacological studies, generally performed in small numbers of patients, indicate that the effects of long term treatment with ACE inhibitors, calcium channel antagonists and some β-blockers on arterial stiffness are generally similar. The effectiveness of an antihypertensive agent in reducing arterial stiffness may also be influenced by the genetic background of the patient. Recently, the Complior® Study has shown the feasibility to assess arterial stiffness in clinical trials involving large populations using an automatic device for measuring PWV. Long term treatment with an ACE inhibitor, perindopril, was associated with a decrease in blood pressure and aortic PWV in patients with essential hypertension. In high risk patients with end-stage renal failure, ACE inhibitors effectively decreased arterial stiffness and had a favorable effect on survival which was independent of changes in blood pressure. The correlation between reversion of arterial stiffness and decrease in cardiovascular morbidity and mortality needs to be confirmed in populations of patients with lower cardiovascular risk.     

冠心病患者脉搏波传导速度与血浆脑钠肽水平的相关性研究

目的探讨冠心病患者脉搏波传导速度（PWV）与血浆脑钠肽（BNP）水平的关系。方法 100例符合入选标准的冠心病用VP1000动脉硬化测定仪测量患者脉搏波传导速度及用荧光免疫法定量测定患者血浆中BNP水平。结果对可能影响PWV的因素进行多元线性回归分析,PWV与BNP正相关（r=0.376P〈0.01）。结论对于冠心病患者PWV是BNP的独立影响因素。     

Arterial calcification and stiffness in chronic kidney disease

1. Patients with chronic kidney disease (CKD) demonstrate a high burden of vascular disease. This vascular disease is unusual by way of a preponderance of medial calcification. Further, traditional cardiovascular risk factors fail to fully explain the high cardiovascular event rate in this population. 2. The present review examines the problem of medial calcification and arterial stiffness evident in patients with CKD and explores evidence for its existence and the potential pathological process involved. Many factors are emerging as potential culprits in this disease entity, although the specific roles of components such as fetuin-A, matrix Gla protein, osteopontin and fibroblast growth factor-23 have yet to be determined. Calcium and phosphate balance remains integral to the pathological process. 3. Pulse wave velocity has proven to be a useful tool to assess and follow arterial stiffness in CKD patients and is discussed. 4. Finally, techniques aimed at reducing or reversing arterial calcification and stiffness are discussed, with as yet no definitive answers available.     

生活方式调节对无临床代谢性疾病中年人群C—F PWV及胰岛素抵抗的影响

目的观察生活方式的调节对于改善大动脉僵硬度的意义。方法1300例动脉硬化检测中发现颈-股动脉搏波传导速度（C—F PWV）减慢，但血压、血糖、血脂、体质量指数均正常者650例，进行生活方式的问卷调查，计算危险因素的发生率，枪测空腹胰岛素、计算胰岛素抵抗指数，并给予生活方式干预调节，对比调节前后C—F PWV及胰岛素抵抗情况。结果各危险因素中，调节前后吸烟发生率差异有统计学意义（P〈0．05）；过咸饮食、高脂饮食、食用谷类过多、嗜食甜食、运动量少及过量饮酒调节前后比较，差异有统计学意义（P〈0．01）。生活方式调节后C—F PWV、胰岛素抵抗指数均改善明显，差异有统计学意义（P〈0．05）。结论生活方式的调节能够降低大动脉僵硬度、改善胰岛素抵抗情况，从而预防心脑血管疾病的发生。     

Genome study of kidney disease in the age of post genome-sequencing

The genome-based study of human disease has been developing rapidly with the completion of the human genome project and the remarkable progress of technology. The genetic variation information associated with disease will certainly enable us to discover potential drug targets and to develop personalized medicine. Chronic kidney disease (CKD) is now recognized as a public health problem because its prevalence is increasing all over the world. No treatment can reverse the progression of CKD to end-stage renal disease (ESRD), which requires enormous medical resources. Moreover, CKD is known to be a strong risk factor for cardiovascular disease. In this review, we summarize the genetic studies that have reported a number of disease susceptibility genes and loci for CKD and ESRD. Earlier investigations, mostly by linkage analysis and association analysis with candidate gene approaches, have demonstrated that genetic factors play a crucial role in CKD and ESRD. However, the findings have contributed little great impacts related to drug discovery and diagnostic tool development in kidney diseases: further investigations are necessary to confirm the previously identified susceptibility genes. Recent technological advances will enable us to perform genome-wide association analysis, discover new disease susceptibility genes, and establish novel treatment strategies based on genomic information related to kidney disease.     

Preventing Cardiovascular Outcome in Patients with Renal Impairment

Patients with chronic kidney disease (CKD), ranging from modest renal impairment to dialysis and transplant, have an increased risk for cardiovascular disease (CVD). Patients with CKD have both traditional and non-traditional risk factors for CVD. The role of lipids as risk factors for CVD in these populations has not been firmly established. In a recent prospective controlled trial, it was established that atherogenic lipids are indeed strong risk factors for CVD in renal transplant recipients, and that treatment with a HMG-CoA reductase inhibitor reduced the incidence of cardiac death and myocardial infarction. For patients receiving dialysis, the association between serum lipid levels and cardiovascular outcome is uncertain and there is no evidence from controlled trials that lipid-lowering therapy does have a beneficial effect on cardiovascular outcome in these patients. Atherogenic lipids are probably a risk factor for patients with mild or moderate CKD, and five subgroup analyses have indicated a favorable effect of lipid-lowering therapy on cardiovascular outcome, although we still lack prospective controlled trials in these patients. CVD in patients with CKD has been a neglected area of research.     

Novel drugs and intervention strategies for the treatment of chronic kidney disease

Chronic kidney disease (CKD) is a worldwide health problem. The disease is most often progressive of nature with a high impact on patients and society. It is increasingly recognized that CKD can be detected in the early stages and should be managed as early as possible. Treatment of the cause, but in particular control of the main risk markers, such as high blood pressure, glucose and albuminuria, has been instrumental in delaying the progression to end-stage renal disease (ESRD). However, despite the state of the art therapy, the absolute risk of renal and cardiovascular morbidity and mortality in CKD patients remains devastatingly high. Novel drugs are therefore highly desirable to halt effectively the progressive renal (and cardiovascular) function loss. Recently, several novel strategies have been tested targeting traditional risk factors such as blood pressure (combination therapy of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) and novel mineralocorticoid receptor antagonists) as well as dyslipidaemia (statins) with surprising results. In addition, drug targets specifically related to the kidney, such as vitamin D, uric acid, erythropoietin and phosphate, have been the subject of clinical trials, in some instances with unexpected results. Finally, novel targets including endothelin receptors and inflammatory pathways are increasingly explored as potential avenues to improve renal and cardiovascular protection, albeit that the drugs tested have not been unequivocally successful. In this article we review novel drugs or intervention strategies for the management of CKD, we try to provide explanations for the failure of some promising drugs and hypothesize on the potential success of new strategies.     

活性维生素D提高慢性肾脏病患者生存率

慢性肾脏病(CKD)患者的预期寿命比较短,绝大多数是因为该人群心血管事件的发生率和死亡率比较高。CKD的进展、矿物质紊乱和骨病、维生素D代谢障碍、继发性甲状旁腺功能亢进和血管钙化等疾病,都与CKD患者死亡率高的发病机制相关。活性维生素D在CKD患者中能预防和治疗骨病作用的同时,也具有预防心血管异常及降低蛋白尿和纤维化的潜在作用。CKD患者使用维生素D和维生素D受体激动药(VDRA)主要以血清甲状旁腺激素(PTH)浓度为指导。维生素D治疗CKD患者的25(OH)Vit D缺乏。如果存在甲状旁腺功能亢进,应该使用VDRA治疗,选择性VDRA可以避免高钙磷血症,钙敏感受体激动剂配合VDRA的疗效更佳。     

Endothelial dysfunction and chronic kidney disease: treatment options

Endothelial cells detect physical and chemical changes in the blood vessels, and release various factors to counter these changes to maintain homeostasis. Traditional cardiovascular disease risk factors, such as hypertension, dyslipidemia and diabetes, cause endothelial dysfunction characterized by off-balanced vasodilation/vasoconstriction, increased oxidative stress and inflammation, deregulation of thrombosis and fibrinolysis, abnormal smooth muscle cell proliferation, and a deficient repair mechanism. Patients with chronic kidney disease (CKD) have a much higher risk of cardiovascular disease and mortality than the general population. Endothelial dysfunction is commonly observed in CKD, likely preceding other cardiovascular complications. Lipid-lowering agents, such as statins, improve endothelial functions and are effective in reducing cardiovascular disease risk in the general population, but have not demonstrated comparable efficacy in the CKD patient population. Similarly, antidiabetic agents, such as thiazolidinediones, that improve endothelial function in the general population are less efficacious than expected in slowing disease progression and reducing cardiovascular disease risk in CKD patients. Interestingly, agents that activate the vitamin D receptor (VDR) for the treatment of hyperparathyroidism secondary to CKD are associated with a survival benefit in CKD patients that is likely mediated through the effects of the VDR on modulating key components involved in endothelial dysfunction. However, a randomized, clinical study is required to confirm the survival benefit of VDR activation therapy for CKD patients. Results from clinical studies suggest that managing hypertension alone may not be adequate in slowing CKD progression and its related cardiovascular complications. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers that target the renin-angiotensin system slow CKD progression, possibly due to their effects on improving endothelial function, independent of controlling blood pressure.