甲状腺机能亢进症血管紧张素转化酶活性的变化及其临床意义

血管紧张素转化酶(ACE)可将无活性的血管紧张素Ⅰ转化为血管紧张素Ⅱ。近年来国外曾报道在甲状腺机能亢进症(下简称甲亢)时此酶活性增高,但国内尚未见报告,本文就36例甲亢的血清ACE 活性变化及其临床意义报告如下。     

甲状腺机能亢进的血清血管紧张素转换酶增高

正常时血管紧张素转换酶主要存在于内皮细胞,肾小管和肠刷状缘内,在病理情况下可出现于结节病上皮细胞和高雪氏细胞内,在单核巨噬细胞内可由糖皮质类固醇诱导产生。有报告在甲亢患者中血清血管紧张素转换酶(SACE)可增高。本文报告了SACE与甲状腺疾病和功能关系的研究。并调查甲状腺激素对SACE合成的可能影响,及在甲亢患者中SACE水平变化的可能原因。     

甲状腺功能亢进性心脏病的临床诊断与防治

甲状腺功能亢进性心脏病(甲亢性心脏病)是甲状腺功能亢进(甲亢)常见并发症之一,是内分泌代谢紊乱所致心脏病。由于患者常以心脏病症状就诊,医护人员常将甲亢性心脏病误诊。甲亢性心脏病发病机制包括心肌代谢变化、血流动力学改变、儿茶酚胺活性增强及肾素-血管紧张素-醛固酮系统(RAAS)作用。甲亢性心脏病的临床诊断是在甲亢诊断明确条件下,至少有心脏扩大、心律失常、心力衰竭、左房室瓣脱垂伴心脏病理性杂音其中之一者。但是甲亢性心脏病常缺乏甲亢所表现的高代谢症候群的症状和体征,如警惕性不高易导致误诊和漏诊,特别是中老年患者,因此对甲亢性心脏病患者,应早诊断早治疗。本文对甲亢性心脏病的临床诊治情况进行如下综述。     

口服肾素抑制剂——阿利吉仑的研究进展

肾素-血管紧张素醛固酮系统(RAAS)在高血压、充血性心力衰竭及慢性肾功能衰竭的重要性早已为人们所认识.利用血管紧张素转化酶抑制剂(ACEI)或血管紧张素受体拮抗剂(ARB)对这些疾病能够有益地干预.肾素抑制剂可以在高水平起始位点上阻滞RAAS系统,可提供新的治疗高血压的药物疗法.阿利吉仑(aliskiren)是一种可口服、非蛋白、低分子量的肾素抑制剂,迄今是进展到临床试验Ⅲ期的肾素抑制剂.本文综述阿利吉仑的药理学特性及在临床中的应用进展.     

醛固酮逃逸的研究进展

肾素-血管紧张素-醛固酮系统抑制剂已成为治疗高血压及心力衰竭的主要药物,然而血管紧张素转换酶抑制剂与血管紧张素Ⅱ受体拮抗剂并没有充分的阻断过度激活的肾素-血管紧张素-醛固酮系统。在经过血管紧张素转换酶抑制剂或血管紧张素Ⅱ受体拮抗剂治疗一段时间后,一部分患者血浆醛固酮水平有所升高,即＂醛固酮逃逸现象＂。该现象的发生率及机制,对临床治疗的影响等重要问题一直不完全清楚,现就醛固醛逃逸现象的发生率、机制、在血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂治疗中的区别等在近年的研究进展做一概要的综述。     

心肾综合征研究进展

心肾综合征是指心脏或肾脏急性或慢性功能障碍而导致另一器官的急性或慢性功能损害的临床综合征.根据心肾疾病发病的相互关系将其分为五型.目前认为发病机制与肾素-血管紧张素-醛固酮系统及交感神经系统的过度激活、一氧化氮/氧自由基的失衡、贫血、炎症等相关.心肾综合征的治疗方面尚缺乏大样本临床试验资料,可选择利尿剂、血管紧张素转化酶抑制剂/血管紧张素受体拮抗剂、β-受体阻滞剂、促红细胞生成素等,一些新型药物如选择性腺苷A1受体拮抗剂、血管加压素受体拮抗剂正进入临床,如出现药物抵抗应早期行肾脏替代治疗.     

甲亢患者肾素-血管紧张素系统活性水平的初步探讨

肾素主要产生于肾脏。血管紧张素转换酶(ACE)是一种限速酶,催化血管紧张素Ⅰ(ATI)变成血管紧张素Ⅱ(ATⅡ)。近年来有人报道,甲亢患者血清ACE活性明显升高,且与血清T_3、T_4呈明显正相关;微量元素锌(Zn)是ACE的活性中心;甲亢患者血清Zn高于正常人。我们选择甲亢患者25例,测定血浆肾素活性(PRA)、ATⅡ,血清ACE和Zn的含量,同时测T_3、T_4、促甲状腺素(TSH)及~(131)I吸收率,以观察肾素-血管紧张素系统与甲亢的关系。     

甲状腺和高血压

临床上甲状腺功能亢进或减退的病人时常伴有高血压;反之某些高血压病人特别是肾性高血压常常伴有甲状腺重量增加,~(131)Ⅰ吸收率降低,血 T_3、rT_3降低和促甲状腺素(TSH)上升等一系列甲状腺形态和功能的异常,这显然提示甲状腺和高血压之间可能存在某种联系。近年来对甲状腺激素增多或减少影响肾功能和肾素-血管紧张素-醛固酮系统以及高血压时甲状腺功能的改变等问题引起了极大兴趣。Dzau发现肝脏合成和分泌血管紧张素原的过程受甲状腺激素的调节和控制,更明确了甲状腺功能和高血压、动脉粥样硬化症之间有内在联系。     

血管紧张素转换酶2-血管紧张素1-7-Mas轴的心血管效应

经典的肾素-血管紧张素系统在维持动脉血压平衡,水电解质平衡,调节细胞增殖及分化中起着重要的作用.血管紧张素1-7及其在体内主要的合成酶血管紧张素转换酶2,及其受体Mas绀成的调节轴可产生广泛的生理及病理生理学效应.此轴可拮抗血管紧张素转换酶-血管紧张素Ⅱ-血管紧张素Ⅱ 1型受体调节轴的效应,从而为高血压、心力衰竭等心血管疾病及其他系统疾病的药物治疗提供新的思路和方法.     

慢性心力衰竭治疗新进展——LCZ696!

心力衰竭即心脏的收缩功能和/或舒张功能发生障碍,不能将静脉回心血量充分排出心脏,导致肺循环和/或体循环淤血,从而引起心脏循环障碍症候群。在过去数十年中,都是以血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体阻滞剂、β受体阻滞剂、醛固酮受体拮抗剂为主的药物进行治疗。而在最近,LCZ696作为一种新型血管紧张素受体-脑啡肽酶双重抑制类药物进入我们的视野,它同时具有抑制肾素-血管紧张素-醛固酮系统和脑啡肽酶的双重抑制作用从而治疗慢性心力衰竭。现就该药相关的药理作用、作用机制及临床效果做一综述。     

The renin-angiotensin-aldosterone system and the kidney: effects on kidney disease

The renin-angiotensin-aldosterone system regulates renal vasomotor activity, maintains optimal salt and water homeostasis, and controls tissue growth in the kidney. However, pathologic consequences can result from overactivity of this cascade, involving it in the pathophysiology of kidney disease. An activated renin-angiotensin-aldosterone system promotes both systemic and glomerular capillary hypertension, which can induce hemodynamic injury to the vascular endothelium and glomerulus. In addition, direct profibrotic and proinflammatory actions of angiotensin II and aldosterone may also promote kidney damage. The majority of the untoward effects associated with angiotensin II appear to be mediated through its binding to the angiotensin II type 1 receptor. Aldosterone can also induce renal injury by binding to its receptor in the kidney. An understanding of this system is important to appreciate that inhibitors of this cascade can reduce the progression of chronic kidney disease in proteinuric disease states. Pharmacologic agents that can interfere with this cascade include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists. This paper will provide an overview of the renin-angiotensin system, review its role in kidney disease, examine the renal effects of inhibition of this cascade in experimental animal models, and review clinical studies utilizing renin-angiotensin-aldosterone inhibitors in patients with diabetic and nondiabetic nephropathies.     

Importance of blood pressure reduction for prevention of progression of renal disease

Despite reduction of stroke and coronary mortality rates, progression of renal disease to end stage continues to occur with increasing frequency. Recent studies emphasize common pathways of elevated arterial pressures that produce increased glomerular capillary pressures and increase filtered proteins in the urinary space. Such proteinuria, along with activation of the intrarenal renin-angiotensin system, endothelin, and inflammatory cytokines, magnifies progressive renal injury and fibrosis. Malignant forms of hypertension with severe arteriolar injury and proteinuria can be treated effectively with current antihypertensive regimens with improved patient survival. Several recent studies indicate improved renal outcomes in proteinuric diseases, generally regardless of the specific antihypertensive agent. Recent trials of hypertensive subjects with minimal proteinuria demonstrate slower rates of disease progression than that seen in subjects with proteinuria above 1 gram per day. Reduction of arterial pressures, particularly when it leads to reduced proteinuria, can slow the progression of many renal diseases.     

Angiogenic cytokines in renovascular disease: do they have potential for therapeutic use?

Experimental and clinical studies suggest that the damage of the renal microvascular function and architecture may participate in the early steps of renal injury in chronic renal disease, irrespective of the cause. This supporting evidence has provided the impetus to targeting the renal microvasculature as an attempt to interfere with the progressive nature of the disease process. Chronic renovascular disease is often associated with renal microvascular dysfunction, damage, loss, and defective renal angiogenesis associated with progressive renal dysfunction and damage. It is possible that damage of the renal microvasculature in renovascular disease constitutes an initiating event for renal injury and contributes towards progressive and later on irreversible renal injury. Recent studies have suggested that protection of the renal microcirculation can slow or halt the progression of renal injury in this disease. This brief review will focus on the therapeutic potential and feasibility of using angiogenic cytokines to protect the kidney microvasculature in chronic renovascular disease. There is limited but provocative evidence showing that stimulation of vascular proliferation and repair using vascular endothelial growth factor or hepatocyte growth factor can slow the progression of renal damage, stabilize renal function, and protect the renal parenchyma. Such interventions may potentially constitute a sole strategy to preserve renal function and/or a co-adjuvant tool to improve the success of current therapeutic approaches in renovascular disease.     

Renal sympathetic denervation suppresses de novo podocyte injury and albuminuria in rats with aortic regurgitation

Background The presence of chronic kidney disease is a significant independent risk factor for poor prognosis in patients with chronic heart failure. However, the mechanisms and mediators underlying this interaction are poorly understood. In this study, we tested our hypothesis that chronic cardiac volume overload leads to de novo renal dysfunction by coactivating the sympathetic nervous system and renin-angiotensin system in the kidney. We also examined the therapeutic potential of renal denervation and renin-angiotensin system inhibition to suppress renal injury in chronic heart failure. Methods and Results Sprague-Dawley rats underwent aortic regurgitation and were treated for 6 months with vehicle, olmesartan (an angiotensin Ⅱreceptor blocker), or hydralazine. At 6 months, albuminuria and glomerular podocyte injury were significantly increased in aortic regurgitation rats. These changes were associated with increased urinary angiotensinogen excretion, kidney angiotensin Ⅱ and norepinephrine (NE) levels, and enhanced angiotensinogen and angiotensin type 1a receptor gene expression and oxidative stress in renal cortical tissues. Aortic regurgitation rats with renal denervation had decreased albuminuria and glomerular podocyte injury, which were associated with reduced kidney NE, angiotensinogen, angiotensinⅡ , and oxidative stress. Renal denervation combined with olmesartan prevented podocyte injury and albuminuria induced by aortic regurgitation. Conslusions In this chronic cardiac volume-overload animal model, activation of the sympathetic nervous system augments kidney renin-angiotensin system and oxidative stress, which act as crucial cardiorenal mediators. Renal denervation and olmesartan prevent the onset and progression of renal injury, providing new insight into the treatment of cardiorenal syndrome.     

Mechanisms of Tissue Injury in Renal Artery Stenosis: Ischemia and Beyond

Renal injury distal to an atherosclerotic renovascular obstruction reflects multiple intrinsic factors producing parenchymal tissue injury. Atherosclerotic disease pathways superimposed on renal arterial obstruction may aggravate damage to the kidney and other target organs, and some of the factors activated by renal artery stenosis may in turn accelerate the progression of atherosclerosis. This cross-talk is mediated through amplified activation of renin-angiotensin system, oxidative stress, inflammation, and fibrosis—pathways notoriously involved in renal disease progression. Oxidation of lipids also accelerates the development of fibrosis in the stenotic kidney by amplifying profibrotic mechanisms and disrupting tissue remodeling. The extent to which actual ischemia modulates injury in the stenotic kidney has been controversial, partly because the decrease in renal oxygen consumption usually parallels a decrease in renal blood flow, and because renal vein oxygen pressure in the affected kidney is not decreased. However, recent data using novel methodologies demonstrate that intra-renal oxygenation is heterogeneously affected in different regions of the kidney. Activation of such local injury within the kidney may lead to renal dysfunction and structural injury, and ultimately unfavorable and irreversible renal outcomes. Identification of specific pathways producing progressive renal injury may enable development of targeted interventions to block these pathways and preserve the stenotic kidney.     

Effect of Aldosterone and Mineralocorticoid Receptor Blockade on Vascular Inflammation

Aldosterone, the final product of the renin-angiotensin-aldosterone system, is classically viewed as a regulator of renal sodium and potassium handling, blood volume, and blood pressure. Recent studies suggest that aldosterone can cause microvascular damage, vascular inflammation, oxidative stress and endothelial dysfunction. In animal models, aldosterone-mediated vascular injury in the brain, heart, and kidneys leads to stroke, myocardial injury, and proteinuria. These effects may be modified by dietary salt intake; aldosterone-mediated vascular damage is increased in susceptible animals fed a high-salt diet compared to a low-salt diet despite lower plasma aldosterone levels on the high-salt diet. In humans, there is a growing literature supporting the adverse effects of aldosterone in heart failure, hypertension, left ventricular hypertrophy, and renal disease. Aldosterone receptor antagonists are beneficial even in patients on angiotensin converting enzyme inhibitors and attenuate aldosterone-mediated vascular injury by mechanisms that appear to be independent of changes in systolic blood pressure. This review focuses on the adverse effects of aldosterone on the vascular system and describes our current understanding of the underlying mechanisms for this injury.     

Pleiotropic renal actions of erythropoietin

CONTEXT: Erythropoietin (EPO), which is used clinically as recombinant human EPO (rHuEPO) for anaemia associated with end-stage renal failure and cancer chemotherapy, also has pleiotropic properties. Although EPO and its receptor are primary mediators of the normal physiological response to hypoxia, rHuEPO can provide impressive protection against acute ischaemic injury in several organs and tissues. The longer-acting hyperglycosylated derivative of EPO, darbepoetin-alpha, is also used for anaemia and has pleiotropic properties. However, the ability of EPO or its analogues to act directly to reduce the severity of renal injury associated with chronic renal failure is not known. STARTING POINT: Ferdinand Bahlmann and colleagues (Circulation 2004; 110: 1006-12) investigated whether low-dose subcutaneous darbepoetin-alpha could protect against renal dysfunction and injury in rats with induced chronic renal failure. Given once weekly, the drug improved renal function and reduced histological evidence of renal injury. Treated rats also had greater weight gain than controls, with no change in systemic blood pressure. The drug did not increase packed-cell volume and it improved survival. WHERE NEXT?: Although the pleiotropic actions of rHuEPO can ameliorate ischaemic and nephrotoxic acute renal failure, Bahlmann's work is the first evidence that darbepoetin-alpha reduces the renal dysfunction and injury of chronic renal failure. Thus rHuEPO and its analogues might have a use in patients with different types of renal failure. These pleiotropic actions, seen at lower doses, must be separated from the haemopoietic properties that occur at clinical doses and which, at the highest doses, might lead to unwanted effects. Novel analogues of EPO are devoid of haemopoietic activity but still possess protective properties. Their ability to reduce renal injury and dysfunction awaits investigation.     

Traumatic unilateral renal artery thrombosis and protein C deficiency. A case report

Post traumatic renal artery thrombosis is rarely described in the literature. This pathology can result from stretch injury to inelastic intima of the renal artery, or by the direct flow to the abdomen causing compression injury to the renal artery against the vertebral column. However, the association of this pathology with hematologic diseases (in particular protein C deficit) was never described. We report an observation of a 28-year-old man with an uneventful history who was admitted to the intensive care unit for traumatic head injury associated with post traumatic renal artery thrombosis requiring nephrectomy. The etiologic investigation of this thrombo-embolic complication reveals a protein C deficit. Our patient was improved under treatment. This original observation confirms that post traumatic renal artery thrombosis can be associated with hematologic diseases (in particular protein C deficit).     

肾脏病患者碱性磷酸酶及同工酶的检测及分析

目的　探讨碱性磷酸酶(ALP)及同工酶与肾脏疾病的关系。方法　1997 -03 ~2003 -05黑龙江省医院用自动生化分析仪测定43例肾脏病患者ALP浓度,聚丙烯酰胺凝胶圆盘电泳及扫描定量测定ALP同工酶浓度。结果　按肾脏病理改变分为肾小球损伤组、肾小管损伤组和重度弥漫病变组。尿液总ALP肾小球损伤组和肾小管损伤组与对照组比较差异有极显著性(P<0 .001),组织非特异型ALP同工酶与正常对照组比较差异有极显著性(P<0. 001);尿液小肠型ALP同工酶肾小管损伤组与正常对照组和肾小球损伤组比较差异有极显著性(P<0. 001)。严重病变组尿液总ALP及同工酶与正常对照组比较差异无显著性(P>0. 05 )。结论　尿液ALP同工酶可以作为肾脏不同部位损伤的指标。