摘要:

Purpose of reviewTo characterize the pharmacokinetics and pharmacodynamics of the different calcium-channel blockers.Recent findingsCalcium-channel blockers have been in use for some time in the end-stage renal disease population. Their primary use has been as antihypertensive and antianginal therapies. In this regard, they are effective agents. Recently, it has been noted that dialysis-related hypotension occurs less frequently in calcium-channel blocker treated patients. Also, access patency and overall patient survival are improved with calcium-channel blocker therapy.SummaryCalcium-channel blockers are useful agents for the control of hypertension in end-stage renal disease patients and appear to favorably influence survival in this population. Calcium-channel blockers are not dialyzable and their pharmacokinetics do not substantially change with renal failure therefore they do not require dose adjustment based on level of renal function. Too few studies exist to determine if individual calcium-channel blockers differ in their effects. Prospective, randomized, controlled clinical trials are needed in the end-stage renal disease population to better understand the role of calcium-channel blockers in the excess cardiovascular disease burden of this population.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThe present review assesses recent publications, from 2001 until the present, which address the relationship between cardiovascular disease (CVD) and anaemia in patients with chronic kidney disease.Recent findingsInsights from the recently published basic science literature have helped to place findings from clinical studies into a new context, and thereby assist us to understand and further explore the complex relationship between haemoglobin level and survival in chronic kidney disease. The effects of erythropoietin molecules and the presence of receptors in vascular endothelium, mycoardium and other tissues are described. Both observational and interventional clinical studies are examined, and limitations in the methodology and statistical analysis of clinical studies are emphasized, but are given context within the body of literature preceding the past year's publications.SummaryData suggest that development of CVD in patients with kidney disease is multifactorial. Several factors associated with CVD are also associated with anaemia, thereby making causal arguments for the role of anaemia in CVD and survival difficult. Arguments are made for the importance of prevention of anaemia and of individualizing therapeutic goals for its treatment. Well designed prospective studies with both CVD events and mortality as outcomes, and with enrolment beginning before the start of dialysis, are essential if we are to determine the optimal therapeutic strategies.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewAbout a dozen controlled clinical trials examined the effect of anaemia correction on the progression of chronic kidney disease. None of these studies fulfilled the stringent criteria of a randomized controlled trial as suggested by the CONSORT statement, yet evidence emerged that anaemia sustains mitogenic and fibrogenic stimuli by lowering local partial oxygen tension. This review addresses the question of why and how anaemia could possibly enhance the progression of chronic kidney disease, and summarizes relevant clinical trials.Recent findingsThe discovery of hypoxia-inducible factor, a transcription factor stabilized under hypoxic conditions, with DNA-binding properties towards about 50 target genes including erythropoietin, has largely encouraged the hypothesis that tissue hypoxia may serve as another common mechanism for the progression of chronic kidney disease besides hypertension or proteinuria. In addition, anaemia-mediated alterations of renal sympathetic nerve activity and anaemia-related increments of oxidative stress may contribute to a progressive nephron loss. Conclusive evidence from clinical trials is scarce.SummaryPathophysiological concepts suggest some impact of anaemia on the progression of chronic kidney disease. The urge for more sound clinical intervention trials is met by the ongoing ECAP study (Effect of early Correction of Anaemia on the Progression of chronic kidney disease).

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of ReviewIn this article we will examine the basis for using chronic high dose parenteral iron therapy in dialysis patients.Recent findingsThere are increasing data that dialysis patients fare better in many respects if they have higher hematocrit values although the real optimal hematocrit has not been defined. There is an increasing tendency to use parenteral iron to achieve this goal.SummaryAlthough parenteral iron achieves seemingly favourable short results, there are no data for its safety in the long term. On the contrary, there are reasons to suggest possible iron overload with chronic use.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewHyperaldosteronism in its various forms is a recognized secondary cause of hypertension, yet the frequency of these disorders and the appropriate evaluation of suspected patients remain controversial. This review will summarize recent literature concerning the frequency of hyperaldosteronism in the hypertensive population, insight from uncommon forms of hyperaldosteronism, and new developments in the diagnosis and treatment of this condition.Recent findingsSeveral series report that around 10% of hypertensive patients have some form of hyperaldosteronism, but aldosterone-producing adenomas are rare. Diagnostic criteria for idiopathic hyperaldosteronism remain controversial, as is the wisdom of widespread screening. Patients with even mild hyperaldosteronism, however, which could be a continuum with low-renin hypertension, may respond exceptionally well to mineralocorticoid antagonism. Eplerenone, a new mineralocorticoid receptor antagonist without antiandrogen side effects, has been an effective antihypertensive in clinical trials and appears to be particularly suitable for low-renin hypertensives. Accumulating evidence suggests that aldosterone excess is cardiotoxic and nephrotoxic, suggesting that mineralocorticoid blockade has specific benefits beyond blood pressure reduction. For patients with severe, confirmed hyperaldosteronism, selective adrenal vein sampling is the only reliable method for determining the source of the aldosterone.SummaryHyperaldosteronism, when defined with liberal criteria, could account for a substantial portion of hypertension. Few of these patients will harbor adrenal adenomas, but those with severe hypertension and hypokalemia often require adrenal vein sampling to direct surgery. With more precise diagnostic strategies, better treatments, and evolving evidence of pathological consequences of aldosterone excess, subtle disorders of aldosterone excess demand precise definition and specific treatment.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewInterruption of the renin-angiotensin-aldosterone system, chiefly with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, has yielded beneficial results in retarding injury and progression in numerous intrinsic renal diseases. The renoprotection offered by these agents is incomplete and far from optimal. Studying mediators of progression other than angiotensin II is therefore extremely important. The emerging role of aldosterone in progression of renal disease and the utility of its antagonism is discussed here.Recent findingsThe experimental evidence linking aldosterone to renal disease is discussed. The exciting results from clinical studies employing mineralocorticoid receptor blockers are also described.SummaryAldosterone antagonism offers additional antiproteinuric benefits to those achieved with angiotensin-converting enzyme inhibition. Long-term trials addressing effectiveness and safety, especially in regards to hyperkalemia, are greatly needed.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewTransmission of external signals from the cell surface to the internal cellular environment occurs via tightly controlled complex transduction pathways. Alterations in these highly regulated signalling cascades in vascular smooth cells may play a fundamental role in the structural, mechanical and functional abnormalities that underlie vascular pathological processes in hypertension. The present review focuses on recent developments relating to two novel signalling pathways: angiotensin II signalling through tyrosine kinases; and oxidative stress and redox-dependent signal transduction. These pathways are emerging as critical mediators of hypertensive vascular disease because they influence multiple cellular responses that are involved in structural remodelling, vascular inflammation and altered tone.Recent findingsA recent advance in the field of angiotensin II signalling was the demonstration that, in addition to its vasoconstrictor properties, angiotensin II has potent mitogenic-like and proinflammatory-like characteristics. These actions are mediated through phosphorylation of both nonreceptor tyrosine kinases and receptor tyrosine kinases. It is also becoming increasingly apparent that many signalling events that underlie abnormal vascular function in hypertension are influenced by changes in intracellular redox status. In particular, increased bioavailability of reactive oxygen species (oxidative stress) stimulates growth-signalling pathways, induces expression of proinflammatory genes, alters contraction-excitation coupling and impairs endothelial function.SummaryA better understanding of the molecular pathways that regulate vascular smooth muscle cell function will provide further insights into the pathophysiological mechanisms that contribute to vascular changes and end-organ damage associated with high blood pressure, and could permit identification of potential novel therapeutic targets in the prevention and management of hypertension.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of the reviewInappropriate sympathetic overactivity is consistently observed in patients with essential hypertension. The present review summarizes the recent advances that have been made in our understanding of the role of the sympathetic nervous system in hypertension.Recent findingsStudies in patients with autonomic disorders underscore the role of the sympathetic nervous system in the long-term maintenance of hypertension. Abnormalities in the afferent limb of the sympathetic nervous system, in the regulation of central neurons where sympathetic outflow originates, and in the modulation of efferent sympathetic function, can all produce autonomic disorders that are associated with hypertension. More subtle dysfunctions in any of these components have been described in essential hypertension and can contribute to its pathogenesis. These include impaired buffering capacity of arterial baroreflexes, increased central sympathetic outflow, and enhanced norepinephrine release (or decrease reuptake) from sympathetic nerve terminals. Whether genetic polymorphisms of adrenoreceptors are associated with essential hypertension is an area of active research.SummaryIncreased sympathetic activity can contribute to sustained hypertension not only because of its hemodynamic effects (increased cardiac output and vascular resistance), but also by altering renal and water handling by the kidney, and by inducing cardiac and vascular remodeling. Antihypertensive agents that directly or indirectly target this sympathetic overactivity may be particularly useful in long-term treatment of essential hypertension.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewIn this review, we summarize the more recent clinical evidence highlighting the importance of vascular inflammation in terms of clinical risk prediction, and the mechanisms mediating the upregulation of inflammatory mediators in cardiovascular disease and hypertension.Recent findingsMarkers of inflammation have been shown to be upregulated in different forms of cardiovascular disease, and to correlate with vascular risk. Atherosclerosis is characterized by chronic inflammation of the vascular wall. The I-κB/nuclear factor-κB system is considered a major intracellular inflammatory pathway, mediating most of the vascular inflammatory responses. Increasing evidence indicates that hypertension, through the vasoactive peptides angiotensin and endothelin-1, promotes and accelerates the atherosclerotic process via inflammatory mechanisms. In animal and human studies proinflammatory properties of angiotensin II have been demonstrated in large conduit and small arteries, in the kidney as well as in the heart. The angiotensin II receptors involved in the inflammatory process and the interaction between angiotensin II and nitric oxide in mediating vascular inflammation have been identified. In addition, recent advances concerning the role of endothelin-1 as another important mediator of chronic inflammation in the vascular wall has been documented, and the relationship between endothelin-1 and angiotensin II on vascular inflammation demonstrated.SummaryInflammatory mechanisms are important participants in the pathophysiology of hypertension and cardiovascular disease. The identification of useful markers of inflammation, of new therapeutic targets to interfere with these mechanisms, and the evaluation of the efficacy of antiinflammatory treatments will allow progress in our ability to combat cardiovascular disease and the complications of hypertension.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewDefective transduction of the dopamine receptor signal in the kidney has been shown to be important in the pathogenesis of hypertension This review will discuss the genetic mechanism for the defective renal dopaminergic function and the interaction with other gene variant products in the pathogenesis of salt sensitivity and essential hypertension.Recent findingsSingle nucleotide polymorphisms of G protein-coupled receptor kinase type 4 (GRK4) phosphorylate, desensitize, and diminish the inhibitory action of D1receptors on sodium transport in the kidney. Inhibition of GRK4 expression normalizes renal proximal tubule D1receptor function in humans and rodents and ameliorates the hypertension in genetically hypertensive rats. Expression of the GRK4 variant, GRK4γA142V, produces hypertension and impairs the natriuretic effect of D1receptor stimulation in mice. In humans, GRK4 single nucleotide polymorphisms are associated with essential hypertension, particularly salt sensitive hypertension. The prediction of the hypertensive phenotype is most accurate when elements of the renin-angiotensin system and GRK4 are included in the analysis.SummaryGRK4 single nucleotide polymorphisms, by preventing the natriuretic function of the dopaminergic system and by allowing the antinatriuretic function of angiotensin II type 1 receptors to predominate, may be responsible for salt sensitivity. Hypertension develops with additional perturbations caused by the variants of other genes (e.g., α-adducin, angiotensin converting enzyme, angiotensinogen, angiotensin II type 1 receptor, aldosterone synthase, 11β-hydroxysteroid dehydrogenase type 2), the quantitative interaction of which may vary depending upon the genetic background.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID