Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular events are the main cause of death in patients with chronic renal failure who are treated with hemodialysis. Hypertension is frequent among dialysis patients and may be a major cause of mortality, although epidemiological studies are controversial in this regard. This disparity in results may be the consequence of an inadequate definition of hypertension in dialysis patients as well as the interaction with hypertension with other risk factors such as malnutrition or left ventricular hypertrophy (LVH), which are strong predictors of death. Although the goal of blood pressure in dialysis has not been established yet, it seems that predialysis blood pressure levels lower than 150/90 mm Hg must be achieved for patients to avoid complications. LVH is very frequent among dialysis patients and starts early in the progression of chronic renal failure. Hypertension is the main cause for its development, but other potentially reversible factors such as anemia, volume overload, secondary hyperparathyroidism, dose of dialysis or malnutrition may also be implicated. Hence, an adequate management of patients on hemodialysis must include the strict control of blood pressure, preferably with angiotensin converting enzyme (ACE) inhibitors, together with those early measures in order to avoid the development of the other causes of LVH or to treat them when they already exist.
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PMID:Blood pressure, left ventricular hypertrophy and long-term prognosis in hemodialysis patients. 983 91

Since the discovery at the end of the seventies of angiotensin converting enzyme inhibitors (ACEI), numerous clinical data became available in the indications for which these agents were initialy developed, taking into account the putative role of renin angiotensin system: first in severe hypertension, secondly in moderate hypertension and then in heart failure. At the same time, an increasing interest was raised for "evidence based medicine" leading to a change in clinical study design: from clinical documentation of effects based on intermediate end points such as blood pressure, serum lipids, serum electrolytes or physical training capabilities to clear demonstrations through double blind placebo controlled trial with a positive effect on morbi-mortality. This evolution was furthermore stimulated by advances of knowledge on physiopathological mechanisms as well as the emergence of new drugs within this therapeutic class both stimulating clinical research. In that prospective, three examples are obvious: treatment of myocardial infarction, slowing down of the progression of diabetic nephropathy and of chronic renal failure. All these new indications for ACEI were obtained though large morbi-mortality clinical studies which are reviewed in this article. Finally, clinical studies are running with ACEI in order to demonstrate a possible effect on primary or secondary prevention of cardiovascular morbi-mortality in high risk populations results which should be available at the beginning of the next century.
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PMID:[Conversion enzyme inhibitors against the progression of renal and vascular diseases: yes but again]. 985 84

One hundred and nine unselected patients with Acute Renal Failure (ARF) of medical aetiology were hospitalized at the Nephrological Unit of Policlinico University Hospital (Modena) during a 30-month period. ARF was considered as a rapid increase of serum creatinine > 2mg/dl over the baseline level or the doubling of pre-existing value in chronic renal failure. Mean age of patients was 67+/-17 years and median age was 72; 64.2% needing dialytic treatment. Four main causes of ARF were identified: 33 patients had reduced renal perfusion by dehydration, hypotension etc.; 20 multifactorial aetiology; 14 biopsy-investigated renal parenchymal diseases and 39 had drug-related acute renal failure (D-ARF). The clinical outcome was significantly worse in elderly patients as regard mortality (P < 0.02), chronic dialytic treatment (P < 0.04) and complete recovery (P < 0.004). The mean age of D-ARF patients was significantly greater than remaining ARF patients (72.6+/-12.8 vs 63.2+/-18.5: P < 0.004. Nonsteroidal antiinflammatory drugs (NSAIDs) and ACE-inhibitors (Ace-i) caused ARF in 24 and 8 patients respectively. Elderly age, vascular disease and monoclonal gammopathy represented the main risk factors and were significantly more frequent in D-ARF patients (P<001, <0.01, <0.04 respectively). Our data confirm the high susceptibility of ageing kidneys to nephrotoxic damage caused by drugs affecting glomerular autoregulation by microvascular mechanisms. Greater attention to renal changes in ageing and an increased dissemination of preventative measures among nephrologists, could reduce the incidence of these serious and potentially lethal diseases.
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PMID:Acute renal failure of medical type in an elderly population. 987 Apr 33

The course of chronic renal failure is generally progressive and mediated by several factors that operate in combination. Several extrarenal events which may cause transient or permanent deterioration of renal function, are important, because their correction may slow the progression of renal disease e.g. volume disorders, infection, nephrotoxic agents. In progression of chronic renal disease leading factors are hypertension, proteinuria and high protein/phosphorus intake. Number of evidence suggests that ameliorating hypertension, reducing proteinuria slow the progression of chronic renal failure. Clinical studies in diabetic nephropathy demonstrated that the renoprotective effect of ACE inhibitors was independent of their effect of systemic blood pressure. In ESRD patients access for renal replacement therapy should be obtained as early as possible. An A-V fistula may take several weeks to mature especially in diabetic or elderly patients. Early dialysis has been advocated in diabetic patients. In general, patients can start ESRD therapy when residual kidney function drops to 5-10% of normal value. High quality of dialysis should be provided to the uremic patient with respect of successful renal transplantation.
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PMID:[Current therapy of chronic renal failure]. 987 58

One of the most important characteristics of chronic renal failure (CRF) is its progression to end stage renal disease. CRF progression depends of many factors indicated in numerous experimental and clinical studies. The present study was undertaken with the aim to examine the role of sex, etiology of CRF, renal function at the beginning of the study, hypertension and protein intake on CRF progression. Ninety-two patients (47 female and 45 male) aged between 17 and 70, with various underlying kidney diseases and various degrees of CRF were followed for 8 years. CRF progression was expressed as Creatinine clearance (CCr) and reciprocal values of serum Creatinine (SCr) against time. CRF progression was slower in women than in men, but not significantly. Patients with diabetic nephropathy (b = 0.00006) and glomerulonephritis (b = 0.00005) had faster progression of CRF than patients with nephrosclerosis (b = 0.00002), tubulointerstitial nephritis (b = 0.00003) and polycystic kidney disease (b = 0.00003). The fastest progression of CRF was in patients with the lowest SCr values at the beginning of the study. Proper regulation of blood pressure was the most important factor in slowing down CRF progression, independently of kind of antihypertensive drugs. Neither angiotensin converting enzyme inhibitors (b = -0.00001) nor calcium channel blockers (b = -0.00002) showed better effects on CRF progression slowing down in comparison with other antihypertensive drugs (b = -0.00001). Low protein diet slowed down CRF progression, but not significantly. In conclusion, our retrospective study confirms that CRF progression depends on sex, underlying renal diseases and serum Creatinine levels at the beginning of the study. Good regulation of blood pressure and low protein diet can slow down CRF progression.
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PMID:Analysis of factors influencing chronic renal failure progression. 1008 78

Complex arrhythmia is frequent in hemodialysis patients but it is not clear if this is a consequence of dialysis or uremia or is secondary to the hemodynamic and cardiovascular alterations often associated with chronic renal failure. The incidence of complex ventricular arrhythmia (frequent multiform premature beats, couplets, and runs) in 31 subjects who had their uremic status recently corrected by renal transplant (Group 1) and in 23 predialysis (Group 2) and 73 hemodialysis (Group 3) chronic renal failure patients were studied with 24-h Holter monitoring. Patients were not receiving antiarrhythmic drugs or digitalis and significant coronary artery disease was excluded by clinical and noninvasive methods. Complex arrhythmia was two times more frequent in dialysis patients but the difference did not reach statistical significance (Group 1: 16%; Group 2: 17%; Group 3: 34%; chi2 4.9, P = .086). The stepwise model of logistic regression analysis identified systolic blood pressure (odds ratio 1.015, 95% confidence interval [CI] 1.001-1.027, P = .03) and left ventricular systolic dysfunction (odds ratio 7.04, 95% CI 1.3-36.7, P = .02) as the only factors that independently influenced the probability of complex arrhythmia. Age, gender, race, diabetes, smoking status, body mass index, diastolic blood pressure, serum creatinine, hematocrit, left ventricular mass index, and use of diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, sympatolytics, and calcium channel blockers did not influence the occurrence of complex arrhythmia. The data indicate that blood pressure and myocardial dysfunction are more important determinants of complex arrhythmia than dialysis or uremia in chronic renal disease patients.
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PMID:Blood pressure and the risk of complex arrhythmia in renal insufficiency, hemodialysis, and renal transplant patients. 1009 Mar 49

Regulation of blood pressure is of crucial importance in the management of patients with chronic renal failure. In the predialysis phase, hypertension is common. Apart from volume overload and an inappropriately activated renin-angiotensin system, overactivity of the sympathetic nervous system appears to play a role as well. Sympathetic outflow may be enhanced by elevated Angiotensin II levels. Maintenance treatment with angiotensin converting enzyme inhibition normalizes sympathetic overactivity in hypertensive patients with chronic renal failure. In view of the unfavourable role of increased sympathetic activity in cardiovascular disease and prognosis, normalization of sympathetic outflow may be a new treatment goal. Hemodialysis is often complicated by sudden hypotension, causing considerable distress and morbidity. Reduction of blood volume causes sympatho-excitation, vasoconstriction and tachycardia. Sudden hypotension, however, is accompanied by acute withdrawal of sympathetic activity, vasodilation and relative bradycardia, also known as the Bezold-Jarisch reflex. Subtle fluctuations in vasomotor tone in hypovolemic conditions can elicit this reflex. In a series of experiments we showed that reduction of blood volume plays a pivotal role in the pathogenesis of hypovolemic hypotension. Autonomic neuropathy and dysfunction of the central opioid system have been proposed as causative mechanisms in dialysis-related hypotension. We, however, could not confirm a pathogenetic role for either mechanism.
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PMID:Regulation of blood pressure in chronic renal failure: determinants of hypertension and dialysis-related hypotension. 1043 50

A lot of evidence points to the important role of the renin-angiotensin system in the physiopathology of hypertension and the progression of chronic renal failure. In this review, the authors report the data concerning the protective effects of antagonists of angiotensin II AT1 receptors (AT1ra). The AT1 ra have been shown to have beneficial effects in most experimental models of nephropathy in which they have been tested (renal ischaemia, essential or induced hypertension, glomerulonephritis, 5/6 nephrectomy, renal transplantation, induced diabetes, toxic and radiotherapy-induced nephropathy). Clinical trials confirm these beneficial effects. In healthy subjects and hypertensive patients, the AT1 ra have identical effects to those of angiotensin converting enzyme (ACE) inhibitors on renal haemodynamics. In hypertensives, Candesartan and Irbesartan increase renal blood flow and the glomerular filtration rate and decrease the filtration fraction. Two studies have also shown that Candesartan and Irbesartan reduce proteinuria in diabetic patients. Similar results have been reported in essential hypertension with renal failure. These data suggest that AT1 ra have beneficial effects on the progression of experimental kidney disease and on proteinuria in the clinical setting. Of the pharmacological agents available for use in this class, it is essential to propose molecules whose efficacy in antagonising the effects of angiotensin II lasts throughout the 24 hour period. Clinical trials are under way to evaluate the effects of AT1 ra on renal function in man over a long period.
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PMID:[Are the antagonists of angiotensin II AT1 receptors protectors of the kidney?]. 1044 11

Life threatening hyperkalaemia (> 7.0 mmol/l) is commonly associated with acute renal failure. Moderate hyperkalaemia (6.1-6.9 mmol/l) is also common and well tolerated in patients with chronic renal failure. Renal failure is the most common cause of hyperkalaemia although other causes to consider include drugs (potassium sparing diuretics, angiotensin converting enzyme inhibitors), hyperglycaemia, rhabdomyolysis and adrenal insufficiency. Hyperkalaemia affects the cardiac conducting tissue and can cause serious arrhythmias including ventricular fibrillation and asystolic arrest. Therefore it is important to treat hyperkalaemia promptly in the emergency department. This paper evaluates the therapeutic options available for treatment of hyperkalaemia.
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PMID:The management of hyperkalaemia in the emergency department. 1190 81

Trandolapril is a newly developed angiotensin converting enzyme inhibitor (ACEI) whose characteristic is that it undergoes hepatic excretion. ACEI appears to have a specific reno-protective and antiproteinuric role in patients with chronic glomerulonephritis(CGN). Although renally excreted ACEI tend to accumulate and cause side-effects in patients with renal dysfunction, the pharmacokinetics of trandolapril were not affected by renal dysfunction. We compared the effect of other renally excreted ACEI with those of trandolapril on serum creatinine (s-Cr), creatinine clearance(Ccr), proteinuria and total protein(TP) in CGN patients who switched from another ACEI to trandolapril. Twelve hypertensive patients with chronic renal failure(nine males and three females, ranging from 30 to 72 years of age) who were treated by other renally excreted ACEIs for long periods(2 to 8 years) with some effects on proteinuria and renal function, were enrolled in the present study. After ACEI therapy, s-Cr had decreased(2.09 to 1.80 mg/dl, p < 0.01) as well as proteinuria(1.65 to 0.71 g/day, p < 0.01). A single daily oral dose of 1 mg of trandolapril was administered to these patients regardless of their blood pressure status and renal functions. After change to trandolapril therapy, s-Cr(2.25 to 2.06 mg/dl, p < 0.01) and urinary protein(1.82 to 1.34 g/day, p < 0.05) significantly decreased. On the contrary, both Ccr and TP significantly increased at the level of 39.4 to 44.4 ml/min(p < 0.05) and 6.80 to 7.02 g/dl (p < 0.01), respectively. No apparent side effects, such as hyperkalemia, hyponatremia, anemia or worsening of the existing renal dysfunction except for coughing, were observed in these patients. Furthermore, none of the 12 patients treated with trandolapril required discontinuation of the compound. In conclusion, it was shown from this study that trandolapril is effective for the treatment of hypertensive patients with renal insufficiency irrespective of the original diseases. Thus, it can be envisaged that trandolapril is one of the most appropriate agents compared to other renally excreted ACEI for these patients with renal insufficiency. We recommend the change from other ACEIs to trandolapril, when renal dysfunction might be due to ACEI accumulation.
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PMID:[Clinical effects of trandolapril in chronic glomerulonephritis patients with renal insufficiency]. 1089 92


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