摘要:

An intense debate has developed as to the risk-benefit ratio of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) following the withdrawal of cerivastatin. The development of rhabdomyolysis in cerivastatin-treated patients should have surprised few since myotoxicity is an accepted class effect of statins. What has sprung from the cerivastatin experience though is a concern for other members of this class. Such misgivings, although understandable, are ill advised. Without question, differences exist in the risk of rhabdomyolysis occurrence amongst the various statins. In this regard, pravastatin and fluvastatin are least likely to produce rhabdomyolysis, which, in part, relates to the fact they are not metabolized by the cytochrome P4503A4 pathway. When muscle damage occurs with statins it is most often the result of a drug-drug interaction rather than a specific adverse response to statin monotherapy. Such drug-drug interactions increase plasma concentrations of a statin and thereby increase the risk of myotoxicity. A growing consensus exists which supports an expanded use of statins in a range of patient groups including the renal failure patient. Polypharmacy and altered drug metabolism increase the risk of myotoxicity, albeit to an ill-defined degree, in this population. Many factors should enter into the choice of a statin in the multiply medicated renal failure patient.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

In renal patients rigorous blood pressure control is crucial to prevent renal and cardiovascular target organ damage. For renoprotection target blood pressure depends on the severity of proteinuria before treatment. For proteinuria of 1-3 g/day a mean arterial pressure of 98 mmHg provides additional benefit, whereas the target should be as low as 92 mmHg if proteinuria exceeds 3 g/day. The antiproteinuric effect of antihypertensive intervention predicts renoprotection; it is therefore recommended that therapy should be titrated not only on blood pressure, but also on reduction of proteinuria. All currently available classes of antihypertensives can be used to reduce blood pressure in renal patients. Interventions based on blockade of the renin-angiotensin-aldosterone system have additional antiproteinuric, and thus renoprotective, potential. Large individual differences in therapeutic benefit are common, even for interventions of proven efficacy at group level. Studies applying different classes of drugs in the same patient (rotation schedules) demonstrate that individual factors are main determinants of therapy response. Exploration of the mechanisms underlying these patient factors is important to improve treatment outcome. Analysis of genetic determinants of therapy response has great potential in this respect. However, therapy response is a complex phenotype. Thus, careful study of gene-gene and gene-environment interactions will be needed in order to turn this type of knowledge into benefit for the patient.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Premature atherosclerosis is a major cause of morbidity and mortality in end-stage renal disease patients. Dyslipidemia and increased oxidative stress contribute to premature atherogenesis in these patients. The dyslipidemia of end-stage renal disease consists of both quantitative and qualitative abnormalities in serum lipoproteins. Qualitative changes include hypertriglyceridemia (increased remnant lipoproteins), low high-density lipoprotein-cholesterol, and increased lipoprotein (a). In addition to quantitative changes, lipoproteins in end-stage renal disease undergo compositional and qualitative changes that make them pro-atherogenic, such as various modifications of apolipoprotein B, including oxidation, and modification by advanced glycation end-products. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and low-dose fibrates could be effective therapies for lipid disorders. The best evidence for increased oxidative stress in end-stage renal disease is the demonstration of increased plasma F2-isoprostanes. Confirmation of the positive findings with high-dose α-tocopherol in the Secondary Prevention with Antioxidants of Cardiovascular Disease in End-stage Renal Disease Study is urgently needed. Clinical trials with statins and other drugs that improve dyslipidemia also need to be undertaken. These therapies could clearly lead to a reduction in cardiovascular morbidity and mortality in these patients.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

When steroids and immunosuppressive drugs were the only available pharmacological agents used to treat membranous nephropathy, nephrologists were polarized into two groups, those supporting therapy on the basis of the results achieved in controlled trials and those opposed to therapy who contended that the side-effects of therapy were too severe to consider in a disease with a relatively benign course. These two groups are drawing closer as treatments with lesser side-effects emerge. The demonstration that proteinuria accelerates progressive kidney failure in all renal diseases led to a major focus on control of proteinuria. Angiotensin-converting enzyme inhibitors, diuretics and angiotensin II receptor antagonists all play a role. Older methods of treatment that reduce proteinuria are being resurrected. A major development is the demonstration in a randomized study that cyclosporin A is effective in membranous nephropathy. Therefore, although there has been no major recent breakthrough or novel therapeutic agent used in membranous nephropathy, a range of new methods of controlling proteinuria provide some compromise between therapeutic enthusiasm and conservative management in this common disorder.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Toxic nephropathy is an important cause of reversible renal injury if detected early. Renal damage can be due to several different mechanisms affecting different segments of the nephron, renal microvasculature or interstitium. Clinical signs may not be apparent in the early stages and assessment of renal function should include thorough evaluation of glomerular filtration rate, proximal and distal tubular function. A kidney biopsy may be indicated to establish the cause and effect relationship. The presence of comorbid conditions such as older age, diabetes mellitus, hypertension and congestive heart failure have a significant influence on the patient's ability to recover from the toxic effects. A significant degree of drug-induced renal toxicity is only acceptable if the causative agent is used for the curative treatment of an underlying disease but not if the aim is the palliative or supportive therapy. The decision to reduce the dose or to stop the toxic agent must be based on the ultimate goal of therapy and the patient's baseline health status.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The interest in daily hemodialysis in the form of short daily hemodialysis and nocturnal hemodialysis has continued to increase over the past few years. A significant number of publications support the evidence for improved outcomes in most of the study areas, including financial benefits. The increased direct cost of the provision of daily hemodialysis seems to be the main obstacle to the wider acceptance of these methods. Convincing data of improved outcomes and evidence of cost efficiency of daily hemodialysis are being generated. These data may increase the interest of the institutional payors as well as of the dialysis industry to create the proper infrastructure for the use of daily hemodialysis. These dialysis regimens promise to have a major impact on the management of end-stage renal disease.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The chemical identification and functional characterization of endothelium-derived hyperpolarizing factors varies depending on vascular size, vascular bed and species. Three major candidates are the epoxyeicosatrienoic acids, cytochrome P450 metabolites of arachidonic acid, potassium ion and hydrogen peroxide. Additionally, electrical coupling through myoendothelial gap junctions serves to conduct electrical changes from the endothelium to the smooth muscle and may mediate or propagate hyperpolarization. Endothelium-derived hyperpolarizing factors are important mediators of vascular relaxation most specifically in resistance sized arteries where they regulate tissue blood flow. The release of the factors is modulated by a number of influences including agonist stimulation, shear stress, estrogen and disease. This article reviews the latest studies concerning the characterization of endothelium-derived hyperpolarizing factors, the mechanisms of factor release and alterations of the factors.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Nitric oxide, the metabolic product of L-arginine by the enzyme nitric oxide synthase, plays a pivotal role in the regulation of vascular homeostasis. Its complex interaction with the autocrine and paracrine systems, particularly angiotensin II, modulates vasoconstriction and vasodilatation as well as the architectural remodeling of the vascular bed. The major vascular hormones known to be involved are angiotensin II and endothelin-1. Upregulation of endothelin-1, a potent molecule, appears to be a consequence of the nitric oxide-angiotensin II imbalance that contributes to end-organ injury. Increased oxidative stress, common to different diseases including diabetes mellitus and hypertension, is also a determinant player in the interaction between angiotensin II and nitric oxide. The influence of a relative malfunction of the nitric oxide system on the vascular tone and vascular structure, and the effects of hypertension on this system, are discussed.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that are expressed in a variety of tissues, including the liver (PPARα), adipose tissue, vascular smooth muscle, the heart, skeletal muscle, and the kidney (PPARγ). PPARδ is expressed ubiquitously. The receptors function as transcription factors to regulate the expression of genes involved in lipid metabolism, cell growth and migration as well as insulin-mediated skeletal muscle glucose uptake. Although the mechanisms by which all these actions occur have not been completely worked out, ligands to these receptors function to improve lipid metabolism, insulin sensitivity, endothelial dysfunction and urinary albumin excretion in patients with diabetes. Thus PPARs appear to have enormous implications for the management of cardiovascular disease.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID