新颖抗高血压药物——口服肾素抑制剂阿利克仑

肾素-血管紧张素-醛固酮系统（RAAS）作为心功能的主要调节者，其重要作用已自拮抗这一系统的药物如血管紧张素转化酶（ACE）抑制剂、血管紧张素受体阻滞剂（ARB）和醛固酮拮抗剂在目前心血管疾病管理中的地位而得到相当佐证。大量临床研究业经确认，醛固酮拮抗剂、     

肾素—血管紧张素系统与肾脏疾病的关系

肾素———血管紧张素系统 (ＲＡＳ)由肾素、血管紧张素原、血管紧张素Ⅰ (Ａｎａｌ)、血管紧张素转换酶 (ＡＣＥ)、血管紧张素Ⅱ (ＡｎｇⅡ )以及血管紧张素受体 (ＡＴＲ)等 6大成分组成 ,其中ＡｎｇⅡ为主要的生物活性肽。本系统在肾脏疾病中的作用几首涉及到肾脏疾病过程中每一方面 ,但最主要的是引起血流动力学紊乱、水盐代谢失调以及促进肾脏疾病进展 ,尤其近年来在几乎所有的肾脏病模型以及大多数临床研究中均一致证实阻断ＲＡＳ能肯定地延缓肾脏疾病进展。此外 ,与此系统密切相关的物质如醛固酮在肾脏疾病中的作用亦越来越多地受到人…     

高血压与肾脏疾病中肾脏局部肾素血管紧张素系统的激活及病理生理作用

肾脏存在独立调节的肾素-血管紧张素系统(RAS).多数高血压与肾脏疾病患者均存在肾脏RAS活性的上调,这对维持机体水钠平衡有重要作用,但同时也促进了高血压的发生,并加速了肾损害的进展.本文结合最近一些基础及临床研究结果,着重讨论疾病状态下肾脏RAS激活的机制、后果及RAS阻断剂的干预意义,这对认识肾脏局部RAS功能,探讨延缓慢性肾脏病进展的治疗策略具有重要意义.     

ARB联合ACEI治疗慢性肾脏疾病的概况

<正>美国肾脏病基金会(NKF)制定的《慢性肾脏病临床实践指南》(Kidney Disease Outcome Quality Initiative,K/DOQI)[1]提出的慢性肾脏疾病(chronic kidney disease,CKD)是指至少3个月期间肾脏损伤(肾脏结构或功能异常),伴或不伴估     

肾素血管紧张素系统与糖尿病肾病相关性研究进展

肾素血管紧张素系统是生理功能颇为复杂的内分泌系统,对糖尿病肾病的发生、发展有重要影响.     

维生素D治疗糖尿病肾病的临床观察

<正>糖尿病肾病(DN)是糖尿病患者死亡的主要原因之一,随着生活方式和饮食习惯的改变,糖尿病的发病率逐年上升,DN成为终末期肾脏疾病的主要原因之一。目前尚缺乏有效的治疗手段,基于阻断肾素-血管紧张素系统(RAS),减少肾小球内压力和蛋白尿的理论基础,血管紧张素转换酶抑制剂(ACEI)、血管紧张素受体拮抗剂(ARB)被广泛用于治疗DN,     

ARB与糖尿病肾病

肾素-血管紧张素-醛固酮系统(RAAS)激活在糖尿病肾病(DN)的发生发展中具有重要意义。临床前及临床试验都证明:RAAS阻断药物——管紧张素Ⅱ(AngⅡ)受体拮抗剂(ARB)具有独立于降压效应的多重肾脏保护作用。虽然从各种机制上看ARB可能优于血管紧张素转换酶抑制剂(ACEI),但是目前的研究未能证明ARB在降低尿蛋白、延缓肾功能损害方面比ACEI具有优越性。越来越多的研究证明ACEI合用ARB比单用药物具有更大的保护作用,所以两者合用达到RAAS双重阻断成为新趋势。新的研究还证明ARB肾脏保护作用可能与血管紧张素转换酶(ACE)的基因多态现象相关。     

肾素-血管紧张素-醛固酮系统抑制剂多靶点干预治疗高血压的研究进展

肾素-血管紧张素-醛固酮系统(RAAS)是参与高血压发病和维持不可或缺的环节;RAAS抑制剂治疗高血压被临床广泛应用,其中主要包括直接肾素抑制剂、血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂.它们作用于RAAS不同靶点,对RAAS抑制剂有效性的影响及其临床应用地位和意义一直被人们所关注,因此对三者各靶点作用特点的进行总结,以揭示RAAS抑制剂多靶点干预的重要性和意义.     

肾素血管紧张素系统与糖尿病肾病

肾素血管紧张素系统是生理功能颇为复杂的内分泌系统，广泛存在于机体各个组织。该系统的关键基因决定着个体的糖尿病肾病易感性。血管紧张素Ⅱ通过细胞外基质成分合成增多、降解减少而促使肾小球硬化。血管紧张素转化酶抑制剂及血管紧张素受体拮抗刑具有独立于血压的治疗糖尿病肾病的作用。     

肾性贫血的药物治疗进展

肾性贫血是慢性肾脏病的常见并发症,与慢性肾脏病患者预后密切相关。肾性贫血目前的治疗主要集中在促红细胞生成素替代和补充铁剂2个方面,临床上存在贫血患病率高、达标率低等问题。近年来,新兴的铁剂、促红细胞生成素制剂以及针对肾性贫血发病机制新靶点的治疗手段不断用于临床,为肾性贫血的治疗提供了新的选择。本文从肾性贫血的发病机制出发,综述了肾性贫血的药物治疗进展。     

Expert opinion on pharmacotherapy of kidney disease in HIV-infected patients

Introduction: Human immunodeficiency virus (HIV) infection is associated with the development of a wide spectrum of kidney diseases. HIV-associated nephropathy (HIVAN) is the most common cause of chronic kidney disease (CKD) in HIV-infected individuals and predominantly affects patients of African ancestry. HIVAN is a leading cause of end-stage renal disease (ESRD) among African–Americans.

Areas covered: An overview of the spectrum of kidney disease in patients with HIV is given. Current pharmacologic interventions to treat kidney disease in HIV are discussed. This review will enhance knowledge regarding the most common causes of kidney disease in HIV-infected patients. An understanding of the principles related to pharmacotherapy in HIV-infected patients with kidney disease will also be gained.

Expert opinion: Kidney disease is an important cause of morbidity and mortality in HIV-infected patients. The most common cause of chronic kidney disease in this population is HIV-associated nephropathy, which is caused by viral infection of the renal epithelium. Several medications that are commonly used in HIV-infected patients can have adverse effects on the kidneys and the doses of many antiretroviral medications need to be adjusted in patients with impaired renal function.     

Expert opinion on pharmacotherapy of kidney disease in HIV-infected patients

INTRODUCTION: Human immunodeficiency virus (HIV) infection is associated with the development of a wide spectrum of kidney diseases. HIV-associated nephropathy (HIVAN) is the most common cause of chronic kidney disease (CKD) in HIV-infected individuals and predominantly affects patients of African ancestry. HIVAN is a leading cause of end-stage renal disease (ESRD) among African-Americans. AREAS COVERED: An overview of the spectrum of kidney disease in patients with HIV is given. Current pharmacologic interventions to treat kidney disease in HIV are discussed. This review will enhance knowledge regarding the most common causes of kidney disease in HIV-infected patients. An understanding of the principles related to pharmacotherapy in HIV-infected patients with kidney disease will also be gained. EXPERT OPINION: Kidney disease is an important cause of morbidity and mortality in HIV-infected patients. The most common cause of chronic kidney disease in this population is HIV-associated nephropathy, which is caused by viral infection of the renal epithelium. Several medications that are commonly used in HIV-infected patients can have adverse effects on the kidneys and the doses of many antiretroviral medications need to be adjusted in patients with impaired renal function.     

非酒精性脂肪性肝病药物治疗进展及认识

非酒精性脂肪性肝病(NAFLD)是西方国家慢性肝病的首要病因。当代人们不良生活习惯增多,NAFLD的全球发病率逐年增高,我国也有相应增高。临床治疗NAFLD的药物包括降脂药、减肥药、胰岛素增敏剂和抗氧化剂等。本文综述NAFLD的药物治疗进展及认识。     

Rho kinase inhibition in diabetic kidney disease

Small GTPases of the Rho family and their down-stream effectors Rho associated kinases (ROCKs) are the molecules that converge a spectrum of pathophysiological signals triggered by the diabetic milieu and represent promising molecular targets for nephroprotective treatment in diabetes. The review discusses recent studies exploring the consequences of diabetes-induced Rho-ROCK activation in the kidney and the effects of ROCK inhibition (ROCKi) in experimental diabetic kidney disease (DKD). Studies in models of type 1 and type 2 diabetes have indicated blood pressure-independent nephroprotective actions of ROCKi in DKD. The underlying mechanisms include attenuation of diabetes-induced increases in renal expression of prosclerotic cytokines and extracellular matrix, anti-oxidant effects and protection of mitochondrial function, resulting in slower development of glomerulosclerosis and interstitial fibrosis. The studies have also shown antiproteinuric effects of ROCKi that could be related to reductions in permeability of the glomerular barrier and beneficial effects on podocytes. Glomerular haemodynamic mechanisms might also be involved. Despite remaining questions in this field, such as the effects in podocytes later in the course of DKD, specificity of currently available ROCKi, or the roles of individual ROCK isoforms, recent evidence in experimental diabetes suggests that ROCKi might in future broaden the spectrum of treatments available for patients with DKD. This is supported by the evidence generated in models of non-diabetic kidney disease and in clinical studies in patients with various cardiovascular disorders.     

Progress in pharmacotherapy of thrombosis

Excessive coagulation and impaired fibrinolysis lead to many hemostatic disorders, which enhance the risk of development of life-threatening cardiovascular diseases such as myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism, belonging to the most important factors influencing morbidity and mortality in civilized societies. The adverse events induced by currently used drugs, the need for regular monitoring of coagulation parameters, inconvenient, in some cases, route of administration stimulate further search for novel, effective and safe methods of therapies of these disorders. In this paper, we describe those new agents which are now under experimental and clinical study, such us prostanoids, nitroaspirin, GP IIb/IIIa receptor antagonists, thienopyridine derivatives, collagen-GPVI and von Willebrand factor-GPIb-IX contact blockers, direct thrombin inhibitors, inhibitors of thrombin-platelet interactions, factor VII inhibitors and tissue factor-factor VII contact blockers. Based on the available literature, we discuss the possible role of these agents in the future prevention and treatment of thromboembolic diseases.     

Appropriate pharmacotherapy in patients with chronic kidney disease - new approach -

The kidney is the most important organ for the excretion of drugs. It was previously thought that appropriate dosages of these drugs could be easily estimated by evaluating the kidney function of patients and the excretion rate of the drug. However, the pharmacokinetic characteristics of patients with kidney disease are as follows: 1) Active metabolites with a higher polarity can accumulate, which can induce unpredictable adverse effects. For example, over sedation with morphine or the development of the fatal toxic syndrome in the case of allopulinol are due to the accumulation of active metabolites derived from these drugs. 2) Although the renal excretion rate of acetoaminophen is only less than 5%, the accumulation of its glucuronide conjugate during multiple dosing in patients with kidney failure may induce high serum acetoaminophen trough levels via the entero-hepatic circulation. 3) Although the renal excretion rate of the drugs are negligible, a remarkable increase in the serum levels of certain drugs were observed in patients with end stage kidney disease, suggesting a significant reduction in non-renal clearance probably by the accumulation of uremic toxins. For drugs that are likely to be administered to patients with kidney disease, even including drugs that are not excreted by the kidney, a full pharmacokinetic study should be conducted in patients and the results carefully assessed. Information on dosing adjustments for impaired kidney function based on estimated glomerular filtration rates should then be clearly stated in the package insert of the drugs.     

Hyperparathyroidism in chronic kidney disease patients: an update on current pharmacotherapy

Introduction: Secondary hyperparathyroidism is the most common abnormalities of mineral metabolism in chronic kidney disease (CKD), which causes bone disease and vascular calcification, leading to increased risk of mortality.

Areas covered: The aim of this review is to provide an overview of pharmacological therapies for secondary hyperparathyroidism, based on current understanding of the disease.

Expert opinion: The initial event in the pathogenesis of secondary hyperparathyroidism is the phosphorus overload per nephron that lead to the secretion of a new phosphaturic hormone, fibroblast growth factor 23 from the bone. Such an abnormality develops very early in CKD, even without hyperphosphatemia. When hyperphosphatemia develops, phosphate binders are prescribed in many CKD patients. Non-calcium containing binders are gaining popularity because of less risk of excess calcium load; however, no specific superiority in patient-level outcomes has been fully established yet. For the direct control of parathyroid hormone secretion, cinacalcet hydrochloride has become widespread in addition to vitamin D receptor activators. As adverse events related to these therapeutic agents occur occasionally, however, and better adherence is one of the most important determinants of the benefits of the drugs, fewer adverse events as well as more potent therapeutic effects should be aimed in the development of new agents in future.     

State-of-the-art pharmacotherapy for diabetic neuropathy

ABSTRACT

Introduction

The global epidemic of diabetes has led to an epidemic of diabetes complications. Diabetic neuropathy is the most common microvascular complication, of which diabetic peripheral neuropathy (DPN) and autonomic neuropathy (AN) are the most prevalent, affecting ~50% of patients. DPN results in pain with a poor quality of life and a loss of sensation with an increased risk of foot ulceration. Autonomic neuropathy can cause significant morbidity in a minority and is associated with increased mortality. The cornerstone of treatment to prevent or limit the progression of DPN/AN is multifactorial risk factor modification including treatment of glycemia, lipids and blood pressure. Whilst, there are no FDA-approved disease-modifying therapies, there are a number of therapies to relieve symptoms in DPN and AN.