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Biomedical subjects

Murray Epstein

Publications and source records attributed to Murray Epstein.

At least 19 recordsLinked to original sources
PubMed2007

Resistant hypertension: prevalence and evolving concepts.

Resistant hypertension is a common medical disorder. Although the exact incidence of resistant hypertension is not established, estimates derived from recent outcome studies including the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), Valsartan Antihypertensive Long-term Use Evaluation (VALUE), and Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) emphasize that this condition may be more common than previously thought. A major advance in our understanding of the pathogenesis and management of resistant hypertension is the recognition of the importance of aldosterone. Several investigators have postulated a direct role of aldosterone excess as an important mechanism for drug resistance in hypertension. The mechanisms whereby aldosterone elevates BP are complex. It was previously thought that aldosterone produced hypertension primarily by promoting sodium retention with consequent hypervolemia. Recent studies of the effects of aldosterone on vascular smooth muscle have, however, delineated several extrarenal mechanisms whereby aldosterone produces hypertension-primarily by its direct vasoconstrictor effects and by altering vascular compliance. Consequently, aldosterone blockade constitutes an effective intervention for treating resistant hypertension.

Aldosterone↗
PubMed2006

Aldosterone blockade: an emerging strategy for abrogating progressive renal disease.

In recent years, there has been a striking paradigm shift with respect to our understanding of the widespread effects of aldosterone. Whereas the role of angiotensin II in mediating progressive renal disease and heart failure has been documented extensively, more recent evidence has implicated aldosterone as an important pathogenetic factor in addition to angiotensin II in the development of these diseases. The focus of this review is aldosterone and progressive renal dysfunction. The extensive preclinical and clinical evidence supporting the efficacy of aldosterone blockade in abrogating proteinuria is summarized. The frequency and clinical importance of aldosterone "escape" is reviewed. Therapeutic considerations to reduce the incidence of hyperkalemia with aldosterone blockade are discussed. The studies reviewed have several important clinical implications for considering new treatment algorithms for patients with incipient nephropathy. Because full doses of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers attenuate but do not abrogate progression of renal dysfunction, add-on aldosterone blockade therapy may constitute a rational therapeutic strategy for retarding progression of renal disease.

Aldosterone↗
PubMed2006

Relationship between erythropoietin administration and alterations of renin-angiotensin-aldosterone.

The effect of erythropoietin (EPO) administration on the responsiveness of the renin-angiotensin-aldosterone system (RAAS) has not been established. Because patients with chronic kidney disease (CKD) require EPO for their management as CKD progresses, it is important to ascertain whether EPO treatment alters the RAAS. If EPO administration stimulates renin-angiotensin or aldosterone (ALDO) this intervention would mediate cardiovascular and renal injury, and consequently promote cardiovascular events and/or exacerbate the progression of renal disease. We reviewed the available publications investigating the effects of EPO on the RAAS. In CKD patients following EPO administration plasma renin activity (PRA) was unchanged in all three and ALDO was not altered in the two studies in which it was determined. In end-stage renal disease (ESRD) patients undergoing dialysis following EPO administration, four studies reported a decrease in PRA levels whereas the remaining nine disclosed no change in PRA levels. The changes in ALDO levels after EPO administration in ESRD patients were discrepant with two studies reporting an increase, two reporting a decrease and the remaining three disclosing no change.

Erythropoietin↗
PubMed2005

Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors on renal function.

Pleiotropic, or non-lipid-dependent, effects mediated by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have important clinical implications for the cardiovascular (CV) system. Atherosclerosis is an inflammatory process accompanied by increases in levels of plasma inflammatory markers and accumulation of immune cells within atherosclerotic plaques. Statins not only decrease serum lipid levels, but also inhibit signaling molecules at several points in inflammatory pathways. The anti-inflammatory effects and improved endothelial function associated with statin therapy are thought to be partly responsible for the reduction in CV morbidity and mortality. In analogy, patients with chronic kidney disease administered statins for CV risk reduction show evidence of improved renal function. However, whether statins confer similar protective benefits on the kidney has not been established. Several lines of evidence suggest that similar etiologic and pathological processes may be involved in CV and chronic kidney diseases. If inflammation and functional changes in the renovascular endothelium contribute to the progression of kidney disease, statins are likely to be effective in the treatment of renal disease. In this review, we critically consider emerging data indicating that statins may modulate renal function by altering the inflammatory response of the kidney and renal vasculature to dyslipidemia. Whether the amelioration of renal function by statins is separable from the lipid-lowering effects of these drugs still remains to be delineated. Other questions that remain to be addressed and issues that should be investigated also are presented.

Animals↗
PubMed2005

Are 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors renoprotective?

Statins reduce serum cholesterol and cardiovascular morbidity and mortality. The mechanisms for these beneficial effects are reviewed. Altered inflammatory responses and improved endothelial function mediated by statins are thought to be partly responsible for the reduction of morbidity and mortality as a result of cardiovascular events. In analogy, whether statins confer similar benefits on the kidney has not been established. This review critically considers the available data whereby dyslipidemia mediates renal dysfunction by modulating the inflammatory response to diverse cytokines. Also reviewed is the emerging database indicating that statins may modulate renal function by altering the response of the kidney to dyslipidemia.

Coronary Artery Disease↗
PubMed2004

Evolving role of calcium antagonists in the management of hypertension.

What, if anything, should physicians make of these apparently disparate hazards in a group of drugs that they prescribe so widely? The authors, and many of our colleagues, still believe that most patients clearly benefit from the judicious use of calcium antagonists. Reports of several large, powered prospective, randomized outcome studies including ALLHAT commend the use of long-acting calcium antagonists that, by virtue of their ability to attain more gradual and sustained plasma levels, do not evoke reactive sympathetic activation and consequently are safe. Concomitantly, such formulations should promote increased patient compliance and thereby favorably influence hypertension-related morbidity and mortality.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Prevention of radiocontrast-induced nephropathy.

Radiocontrast administration is a common cause of hospital-acquired acute renal failure. It is associated with significant in-hospital and long-term morbidity and mortality and increases the costs of medical care by at least extending the hospital stay. Although individuals with normal renal function generally are not considered to be at particular risk, patients with preexisting renal failure are much more likely to experience this complication after radiocontrast agent administration. Typically, serum creatinine levels begin to increase at 48 to 72 hours, peak at 3 to 5 days, and return to baseline within another 3 to 5 days. A variety of therapeutic interventions, including saline hydration, diuretics, mannitol, calcium channel antagonists, theophylline, endothelin receptor antagonists, and dopamine, have been used in an attempt to prevent radiocontrast-induced nephropathy. Of these, saline hydration is the sole efficacious therapy to protect against radiocontrast-induced nephropathy. Recent advances have examined the impact of fenoldopam (dopamine-1 [DA-1] receptor; DA-1 agonist), the antioxidant N-acetylcysteine, iso-osmolar contrast agents, hemodialysis, and hemofiltration in ameliorating radiocontrast-induced nephropathy. This review focuses on current interventions to ameliorate radiocontrast-induced acute renal failure and provides an analysis of some of the recent studies conducted to halt radiocontrast-induced nephropathy.

Acetylcysteine↗
PubMed2004

Dopamine-1 receptor agonist: renal effects and its potential role in the management of radiocontrast-induced nephropathy.

Radiocontrast-induced nephropathy remains the third leading cause of hospital-acquired acute renal failure. Once established, this syndrome is associated with increased morbidity and mortality as well as increased health care costs. Recently, studies have been initiated to evaluate the potential of a selective dopamine-1 receptor agonist (fenoldopam) in ameliorating radiocontrast-induced renal failure. Selective dopamine-1 receptor agonists exhibit many desirable renal effects that support their use for the prophylaxis of radiocontrast-induced nephropathy, including decreases in renal vascular resistance and increases in renal blood flow, glomerular filtration, and sodium and water excretion. Several reports have documented a beneficial effect of fenoldopam administration in attenuating radiocontrast-induced nephropathy. In contrast, a recent multicenter, randomized study did not demonstrate a renoprotective effect of fenoldopam against radiocontrast-induced nephropathy. The presence of multiple confounders, however, precludes a definitive conclusion regarding the ability of fenoldopam to protect against radiocontrast-induced nephropathy. Additional studies are needed to properly evaluate the role of fenoldopam in radiocontrast-induced nephropathy prophylaxis.

Acute Kidney Injury↗
PubMed2002

The use of calcium antagonists in the treatment of hypertensive persons with kidney disease.

The treatment of hypertension is proven to reduce cardiovascular and renal risk. Combination drug therapy is becoming recognized as a necessity in most patients with hypertension and kidney disease. Allegations about the safe use of calcium antagonists in patients with kidney disease have led to questions and confusion about their use in this common condition. This article reviews the cardiovascular and renal safety of the long-acting calcium antagonists from studies comparing calcium antagonists with placebo and with angiotensin converting enzyme inhibitors or angiotensin receptor blockers in patients with kidney disease and hypertension. Patients with proteinuria and kidney disease should have their blood pressure brought as close to target (< 130/80 mm Hg) as possible for cardiovascular and renal protection. Lowering blood pressure in this setting will require an average of three antihypertensive agents. In patients with hypertension and proteinuria, angiotensin converting enzyme inhibitors or angiotensin receptor blockers must be part of the regimen, and calcium antagonists are safe and effective in this condition when used with them in combination.

Calcium Channel Blockers↗
PubMed2002

Recent landmark clinical trials: how do they modify the therapeutic paradigm?

Despite intense investigation and clinical attention, many challenges remain in the management of the hypertensive patient. It is clear that hypertension remains inadequately controlled worldwide, with the control rate in the United States approximating 27%. Furthermore, several recent studies have underscored that it is frequently difficult to attain control at goal blood pressure (BP) with monotherapy and that adequate control of hypertension based on the newer more intensified BP goals necessitates multiple drug therapy. Indeed, in the recently published landmark trials of angiotensin I receptor antagonists, including the Irbesartan Diabetic Nephropathy Trial (IDNT) and Reduction of Endpoints in Non-insulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL), multiple antihypertensive drugs were required to attain goal. A pivotal class of drug required to comprise this regimen is the calcium antagonists. For example, in RENAAL, 78% of patients randomized to losartan required add-on therapy with a calcium antagonist. Calcium antagonists are an important and often necessary component of this multiple drug regimen.

Antihypertensive Agents↗
PubMed2002

Comparative effects on dynamic renal potassium excretion of ACE inhibition versus angiotensin receptor blockade in hypertensive patients with type II diabetes mellitus.

Both ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) are renoprotective beyond their effects on blood pressure (BP), but their widespread use is limited by their tendency to provoke hyperkalemia. The comparative effects of ACEI and ARB on potassium handling have not been investigated. The objective of this study was to determine whether there are differences in dynamic renal potassium handling between ACEI and ARB in response to an oral potassium challenge. This was a randomized crossover study of candesartan versus lisinopril titrated to control BP followed by an inpatient study of renal potassium handling in 24 hypertensive patients with type II diabetes mellitus (DMII) and preserved renal function. Following an oral potassium challenge (0.75 mmol/kg), differences in hourly serum K (mmol/L), rate of urinary potassium excretion (UkV, micromol/min), and fractional excretion of potassium (FEK) were assessed by repeated-measures ANOVA. Hourly UkV(p = .45) and FEK (p = .19) were similar for candesartan and lisinopril, although FEK at 2 hours for candesartan tended to exceed that for lisinopril (.34 [.04] vs. .26 [.03]) and approached significance (p = .096). UkVfor candesartan at hour 2 was 177 (26) and 121 (21) for lisinopril and also approached significance (p = .10). Serial serum potassium did not differ (p = .70). No statistical differences were discovered in renal potassium handling between candesartan and lisinopril in patients with DMII and preserved renal function. Whether there are differences between the drug classes in renal impairment remains to be determined.

Administration, Oral↗
PubMed2002

Cyclooxygenase-2 expression and function in renal pathophysiology.

Cyclooxygenase (COX) constitutes the rate-limiting enzyme in the biosynthetic cascade of prostaglandin (PG). Evidence has accrued suggesting pathophysiological states with altered COX-2 activity and expression. Recent experimental evidence suggests that COX-2 has a pathogenetic role in some of these derangements. In other situations, the effect of altered COX-2 regulation is unclear or possibly beneficial. These processes suggest new areas for potential use of COX-2-specific inhibitors. Conversely, in some conditions COX-2-specific inhibitors should be avoided. The conventional view is that COX-2 is an inducible enzyme. However, COX-2 is also active in the constitutive production of prostanoids in the kidney. Consequently, the pathophysiological states discussed herein include not only COX-2 induction during inflammation but also derangements in COX-2 expression and function caused by non-inflammatory stimuli.

Animals↗