Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
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In recent years, the ability of the various antihypertensive drugs to provide renal protection has been the subject of increased attention. Whether calcium antagonists prevent or reduce the rate of progression of renal damage is still a matter of controversy. This paper reviews the findings of recent animal and human studies on the haemodynamic and renal protective effects of calcium antagonists. These agents preferentially vasodilate afferent arterioles, leading to an increase in renal blood flow and glomerular filtration rate. These effects are more pronounced in hypertensive patients than in normotensive subjects and persist even when renal function is impaired. In animal models of chronic renal failure, calcium antagonists can reduce glomerulosclerosis. However, the mechanisms involved in their renal protective effect appear to be different from those of angiotensin converting enzyme (ACE) inhibitors as they do not reduce intraglomerular pressure. Renal failure caused by vasoconstriction related to radiocontrast agents or cyclosporine can be partly prevented by the administration of a calcium antagonist. Furthermore, in patients with renal artery stenosis, calcium antagonists reduce blood pressure with less renal blood flow impairment than ACE inhibitors. Preliminary clinical studies suggest that verapamil or diltiazem may reduce proteinuria in hypertensive diabetic patients. Whether these compounds can also retard the progression of renal failure in these patients remains to be established with larger trials.
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PMID:Renal haemodynamic and protective effects of calcium antagonists in hypertension. 886 98

The aim of this study was to evaluate the prevalence of renal artery stenosis in patients with clinical signs of peripheral vascular disease and hypertension. One hundred patients, mean age 69 years (range 45-88) with symptoms and clinical signs of severe peripheral ischemia, underwent aortography to determine the degree of peripheral vascular disease and possible renal artery stenosis. History of claudication, and measurement of systolic distal blood pressure (BP) and calculation of the Ankle Brachial Index was used to define the severity of peripheral vascular disease. A total of 31% had renal artery stenosis (14% greater than 50% reduction in luminal diameter). In a subgroup of patients with hypertension and peripheral vascular disease (n = 74), 34% had renal artery stenosis. In the subgroup of patients with renal artery stenosis, 81% have hypertension. Patients with renal artery stenosis and lumen reduction of more than 50%, 93% have hypertension (P < or = 0.001). In conclusion this study shows that the combination of peripheral vascular disease and hypertension is an important clinical clue for renovascular disease. Examination for reno-vascular disease in this population should be considered, since the prevalence of the condition is high. Furthermore examination for renal vascular disease in this population is mandatory, before treatment with angiotensin converting enzyme (ACE) inhibitors is initiated, since treatment might lead to serious renal function impairment.
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PMID:Prevalence of renal artery stenosis in patients with peripheral vascular disease and hypertension. 886 60

Noninvasive diagnostic methods for evaluation of renal arteries continue to improve. Contrast arteriography is the reference standard to which other techniques are compared, and preoperative arteriography before operative or endovascular therapy remains the practice standard. However, noninvasive examination methods have supplanted arteriography as a screening test for renal artery occlusive disease, and they allow more selective use of the invasive technique. ACE inhibitor-enhanced renal scintigraphy has improved on the sensitivity of standard renal scintigraphy, but several investigators found it still lacks when significant renal dysfunction is present. A positive scan implies the renal artery lesion is functionally significant and is predictive of a response to therapy. Although ACE inhibitor-enhanced renal scintigraphy can detect significant renal artery disease, it can neither localize the arterial lesion nor can it characterize the severity of the stenosis. Renal scintigraphy therefore lacks utility as a method to follow progression of the arterial disease. Magnetic resonance and helical CT imaging are advanced technologies that acquire axial imaging data, but with advanced software and powerful image processing hardware, the anatomic information can be represented in multiple planes or with three-dimensional reconstructions. The anatomic information provided is not limited to the renal arteries, but can define relationships to the surrounding anatomy. Validation studies from several institutions suggest that although these methods for renal artery assessment may be sufficiently accurate for screening use, they remain relatively expensive and are just now becoming more widely available. Not all patients can be studied. Helical CT scanning requires a relatively large intravenous contrast dose, which is undesirable in patients with renal insufficiency, and it seems to underestimate severity of some renal artery stenoses. MRA is impractical or unsafe for patients with claustrophobia, cardiac dysrhythmias, pacemakers, certain types of metallic implants or clips, or for seriously ill patients requiring monitoring. Duplex scanning is both sensitive and specific. It is the least expensive of the available diagnostic modalities, and it is completely safe and noninvasive. Not only is the presence of a renal artery lesion detectable, the severity of the stenosis can be categorized and its hemodynamic significance or renal blood flow can be evaluated. Renal artery duplex scanning is the optimal method for renal artery assessment when it is available from a validated vascular laboratory. However, this last point is the key. The utility of the study is entirely dependent on the skill and experience of the examining technologist. Other drawbacks to duplex scanning include the fact that to yield the "whole picture" of the anatomy and pathology requires a mental synthesis. Real-time scanning generates a series of images and flow data that must be interpreted with a understanding of how the scan was performed. Clinical circumstances, local expertise, equipment availability, costs, and other important considerations will factor into the decision-making process of planning a work-up for suspected renal artery stenosis. The noninvasive diagnostic technologies continue to advance, and as new methods are validated, the need for arteriography may be further lessened.
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PMID:Noninvasive assessment of renal artery stenosis. 889 15

Arterial hypertension may favour the progression of non-diabetic primary renal disease and participate in the appearance of atheromatous renovascular disease. In AIPRI trial (ACE-inhibition in the progression of renal insufficiency) the ACE-inhibitor benazepril was able to protect patients with mild-to-moderate renal disease against the progression of renal insufficiency. Some clinical observations suggest that in many aged patients with long-standing hypertension the appearance of renal failure may be related to atheromatous reno-vascular disease. This disease may be responsible for progressive renal failure through renal artery stenosis and/or cholesterol microembolization.
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PMID:Recent data on hypertension and progressive renal disease. 900 94

Treatment with ACE inhibitors results in kidney protection due to reduction of systemic blood pressure, intraglomerular pressure, an antiproliferative effect, reduction of proteinuria and a lipid-lowering effect in proteinuric patients (secondary due to reduction of protein excretion). Elderly patients with diabetes melitus, coronary heart disease or peripheral vascular occlusion are at risk for deterioration of kidney function due to a high frequency of renal artery stenosis in these patients. In patients with renal insufficiency dose reduction of ACE inhibitors is necessary (exception: fosinopril) but more important is the risk for development of hyperkalemia. Patients at risk for renal artery stenosis and patients pretreated with diuretics should receive a low ACE inhibitor dosage initially ("start low - go slow"). For compliance reasons once daily ACE inhibitor dosage is recommended.
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PMID:[ACE inhibitors and the kidney]. 903 82

FUNCTIONAL DIAGNOSTIC TESTS FOR SELECTING PATIENTS FOR RENAL ARTERIOGRAPHY: The functional diagnostic tests now available to select patients for renal arteriography, such as captopril-renal scintigraphy and the captopril-peripheral vein renin test, have a high degree of diagnostic accuracy, 70% sensitivity at 90% specificity, but they are still not good enough to assess the large population of hypertensives for renal artery stenosis. The use of the angiotensin converting enzyme (ACE) inhibitor challenge and the introduction of a new pharmacon, technetium-labelled mercapto-triglycine, have not sufficiently increased the value of scintigraphy and further improvement in the near future seems unlikely. THE USE OF CLINICAL CRITERIA TO IDENTIFY HIGH-RISK PATIENTS: A more realistic approach to the diagnosis of renal artery stenosis is to seek simple and sensible clinical criteria to identify high-risk patients. The blood pressure response to 2 months of treatment with a standardized two-drug regimen is a suitable criterion. Interim analysis of an ongoing prospective multicentre study in the Netherlands indicates that the prevalence of renal artery stenosis is as high as 25% in patients who are resistant to the combination of 10 mg amlodipine + 50 mg atenolol, compared with 15% in patients resistant to the combination of 20 mg enalapril + 25 mg hydrochlorothiazide. When drug resistance is used as the selection criterion for arteriography, the total number of cases detected with intra-arterial digital subtraction angiography does not seem to differ according to which of these drug regimens is used. FUTURE POSSIBILITIES: The current enthusiasm for percutaneous transluminal renal angioplasty (PTRA) and stenting may be premature. With further improvement of non-invasive techniques to visualize the renal arteries, such as colour Doppler ultrasound with microparticle contrast enhancement or magnetic resonance angiography, it should become more attractive to follow patients with renal artery stenosis while they are being treated with drugs rather than automatically resorting to PTRA.
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PMID:Renal artery stenosis towards the year 2000. 912 Jun 74

We report the case of a 63 year old hypertensive male who presented with acute renal failure following treatment of his hypertension with the ACE antagonist, captopril. He was documented to have bilateral renal artery stenosis, which was treated by left renal artery angioplasty and revascularisation of the right kidney by anastomosis of the right renal artery to the superior gastroduodenal branch of the hepatic artery. Postoperatively, he made an excellent recovery, with restoration of his renal function to normal and improved control of his hypertension.
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PMID:Renal revascularisation by gastroduodenal-renal bypass as treatment of renal artery stenosis. 923 May 57

The aim of the study was to evaluate the effect of angiotensin converting enzyme inhibition on blood pressure and plasma renin activity (PRA) in patients with essential (EH) and renovascular (RVH) hypertension. Forty patients with RVH and sixty four with EH were studied. All patients underwent renal digital subtraction angiography in order to find out renal artery stenosis. Blood pressure was measured before and 15, 30, 45, 60 and 90 minutes after captopril administration in the captopril test. PRA was determined before and 60 minutes after captopril. It was shown that fall of systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressure after captopril was significant in each time period both in EH and RVH. Hypotensive effect was significantly higher (p < 0.001) in RVH. Basic PRA did not differ in the studied groups. 60 minutes after captopril administration PRA was significantly higher (p < 0.001) in patients with RVH. Absolute and percentage rise of PRA also differentiated studied groups (p < 0.001). Significant correlations were found between the change of PRA after captopril and fall of SAP, DAP and MAP in both groups. These relationships were stronger in RVH.
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PMID:[Usefulness of converting enzyme inhibitors in diagnosis of renovascular hypertension. I. Comparison of the effect of angiotensin converting enzyme inhibition on blood pressure and plasma renin activity in patients with primary hypertension and renovascular hypertension]. 938 Aug 5

Renal artery stenosis has become increasingly common as a cause of refractory hypertension and renal insufficiency. There is a high prevalence of bilateral disease and the lesions tend to progress over time. Newer, less invasive, imaging modalities such as doppler ultrasound, magnetic resonance angiography, and spiral CT scanning are evolving technologies in the diagnosis of renal artery stenosis. Advances in surgical technique, particularly the development of extra-anatomical procedures such as spleno-renal and hepato-renal by pass, have significantly lowered surgical morbidity and mortality and provides revascularization options for patients with complex vascular disease that would previously not have been considered because of their high surgical risk. Improvements in angioplasty technique and the use of stents are broadening the types of lesions that can be successfully approached with these techniques and may be particularly helpful for patients with more severe cardiac or cerebrovascular disease. The benefits of revascularization may be even greater for preservation of renal function than for control of blood pressure in properly selected patients. It is difficult to predict which patients will benefit from surgical revascularization versus medical management of RAS. Knowledge of the progressive nature of RAS, the high prevalence of bilateral disease, and the clinical characteristics that correlate with progression (e.g., decreasing renal size) are helpful in guiding clinical decisions regarding intervention. Additional studies to determine the predictive value of non-invasive tests such as CRS, doppler ultrasound before and after administration of angiotensin converting enzyme inhibitors, and other tests, are needed to assist the clinician in identifying who will benefit most from revascularization both in terms of renal function and blood pressure control.
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PMID:Medical Grand Rounds: refractory hypertension and renal insufficiency in a patient with renal artery stenosis. 938 40

The aim of this study was to evaluate the prevalence of renal artery stenosis in patients with clinical signs of peripheral vascular disease and hypertension. One hundred patients, mean age 69 years (range 45-88) with symptoms and clinical signs of severe peripheral ischaemia, underwent aortography to determine the degree of peripheral vascular disease and possible renal artery stenosis. History of claudication and measurement of systolic distal blood pressure and calculation of the Ankle Brachial Index was used to define the severity of peripheral vascular disease. Thirty-one percent had renal artery stenosis (14% greater than 50% reduction in luminal diameter). In a subgroup of patients with hypertension and peripheral vascular disease (n = 74), 34% had renal artery stenosis. In the subgroup of patients with renal artery stenosis, 81% had hypertension. Among patients with renal artery stenosis and lumen reduction of more than 50%, 93% had hypertension (p < 0.001). In conclusion this study shows that the combination of peripheral vascular disease and hypertension is an important clinical clue for renovascular disease. Examination for renovascular disease in this population should be considered, since the prevalence of the condition is high. Furthermore, examination for renal vascular disease in this population is mandatory, before treatment with angiotensin converting enzyme inhibitors is initiated, since treatment might lead to serious renal function impairment.
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PMID:[Occurrence of renal artery stenosis in patients with peripheral arteriosclerosis and hypertension]. 941 95


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