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Diagnosis and Management of Atherosclerotic Renal Artery Stenosis: Improving Patient Selection and Outcomes  CME

Christopher J. White, MD; Jeffrey W. Olin, DO

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Summary and Introduction

Summary

Renal artery stenosis (RAS) is common among patients with atherosclerosis, and is found in 20-30% of individuals who undergo diagnostic cardiac catheterization. Renal artery duplex ultrasonography is the diagnostic procedure of choice for screening outpatients for RAS. Percutaneous renal artery stent placement is the preferred method of revascularization for hemodynamically significant RAS, and is favored over balloon angioplasty alone. Stent placement carries a class I recommendation for atherosclerotic RAS according to ACC and AHA guidelines. Discordance exists between the very high (>95%) procedural success rate and the moderate (60-70%) clinical response rate after renal stent placement, which is likely to be a result of poor selection of patients, inadequate angiographic assessment of lesion severity, and the presence of renal parencyhmal disease. Physiologic lesion assessment using translesional pressure gradients, and measurements of biomarkers (e.g. brain natriuretic peptide), or both, could enhance the selection of patients and improve clinical response rates. Longterm patency rates for renal stenting are excellent, with 5-year secondary patency rates greater than 90%. This Review will outline the clinical problem of atherosclerotic RAS and its diagnosis, and will critically assess treatment options and strategies to improve patients' outcomes.

Introduction

Patients with atherosclerotic coronary artery disease or peripheral arterial disease, associated with uncontrolled hypertension or renal insufficiency, are at increased risk for renal artery stenosis (RAS).[1] When selecting patients for renal artery stenting, both functional and anatomical data should be considered to optimize the benefit of revascularization for each individual. Well-accepted indications for renal artery revascularization are outlined in Box 1. Primary stent placement (the practice of deploying a stent regardless of the result of balloon angioplasty as opposed to provisional stent placement, where stenting is performed only if the balloon angioplasty result is poor), has largely replaced surgical therapy in patients with suitable anatomy who do not respond to medical therapy.[2] In this Review, we examine the management of RAS in the context of diagnostic imaging, patient selection to improve the treatment response rate, and procedural safety.

Prevalence of Renal Artery Stenosis

The prevalence of RAS depends upon the population examined. Screening renal duplex ultrasonography (DUS) studies demonstrated RAS (>60% stenosis) in 6.8% of individuals in a Medicare population (mean age 77 years).[3] RAS was present in almost twice as many men as women (9.1% versus 5.5%, P = 0.053), but no differences were noted in the prevalence of RAS between white and African American individuals (6.9% versus 6.7%, P = 0.933). An autopsy series found RAS (≥50% stensosis) in 27% of patients older than 50 years, and the proportion rose to 53% in those with a history of diastolic hypertension (>100 mmHg).[4] RAS is the cause of end-stage renal disease in 10. 15% of patients commencing kidney dialysis,[5,6] and approximately 25% of elderly patients with renal insufficiency have undiagnosed renal artery stenosis.[7-9] In the general hypertensive population, RAS is the most common (2-5%) secondary cause of hypertension.[10]

In the adult population, RAS is predominantly the result of atherosclerosis, although fibromuscular dysplasia—commonly found in young women—is the next most common cause of RAS.[11] The presence of atherosclerosis in another circulatory bed (i.e. cerebral, coronary, or peripheral vascular) increases the likelihood of RAS being present.[12] In patients undergoing cardiac catheterization for suspected coronary artery disease, RAS is found in up to a third of patients (Table 1).[13-17] RAS is present in 30-40% of patients with peripheral artery disease or abdominal aortic aneurysm.[18,19] In a multi variable analysis, Weber-Mzell et al.[14] demonstrated that RAS was more prevalent in patients with extensive coronary artery disease (i.e. multivessel coronary disease) than in patients with single-vessel disease.

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Natural History of Renal Artery Stenosis

Atherosclerotic RAS generally progresses over time and is often associated with loss of renal mass and worsening renal function.[20-24] Progression of RAS lesions is directly related to the underlying severity of stenosis. Progression to occlusion is most likely in patients with severe arterial narrowing (≥60%).[25] Worsening of 'asymptomatic' RAS is associated with a progressive loss of renal function.[20]

Atherosclerotic RAS remains a major cause of end-stage renal disease. In a serial angiographic study, decline in renal function was significantly greater among patients with RAS than in normal control participants, and was related to the severity of RAS.[20] In a study of patients starting dialysis secondary to atherosclerotic RAS, the mean survival time was 25 months, and the 2, 5, and 10 year survival rates were 56%, 18%, and 5%, respectively.[26]

RAS is an independent predictor of adverse cardiovascular events, such as myocardial infarction, stroke, and cardiovascular death.[20,25] Hemodynamically significant RAS is also associated with renal insufficiency, coronary artery disease, peripheral artery disease, hypertension, and cerebrovascular disease. Survival is reduced among patients with severe RAS compared with those with mild or no RAS. In patients identified as having greater than 75% RAS at the time of cardiac catheterization, 4-year survival was 57%, compared with 89% in patients without RAS (P <0.001).[27] Moreover, survival was independent of prior myocardial revascularization procedures, and patients with bilateral RAS had lower 4-year survival than patients with unilateral RAS (47% versus 59%, P <0.001).[28]

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Diagnosis of Renal Artery Stenosis

Noninvasive Assessment

Screening for RAS is appropriate in patients at increased risk for this disease (Box 2). A distinction should be made, however, between identifying patients with RAS who have a very high risk of major cardiovascular events and require aggressive medical management, and the selection of patients for revascularization, which requires a risk-to-benefit analysis and should be made carefully and judiciously following accepted indications for intervention. Whenever possible, noninvasive direct imaging tests (DUS, CT angiography [CTA], and magnetic resonance angiography [MRA]) are preferable to invasive studies. The optimum RAS imaging strategy is outlined in Box 3.

Indirect tests for RAS, such as the captoprilstimulated renal flow scan, the captopril test, and plasma renin assay should be relegated to second-line use because they have poor sensitivity in patients with bilateral renal artery disease or RAS in a single functioning kidney, and in patients with azotemia.[27] Inconclusive results from noninvasive tests should be clarified by performing catheter-based angiography. The hemodynamic severity of RAS should be determined by measuring the translesional pressure gradient.[2]

Ultrasonography. DUS—an excellent method for detecting RAS—is the least expensive of the imaging modalities, is highly dependent on the skill level of the technician, and provides useful information about the location and degree of stenosis, kidney size, and other associated disease processes such as obstruction. DUS can be performed without altering the patient's antihypertensive regimen, and does not require administration of potentially toxic contrast agents, all of which makes it the imaging procedure of choice.

Figure 1 demonstrates a severe stenosis of the left renal artery before and after renal artery stent implantation. Compared with MRA, DUS has a sensitivity of 84-98% and specificity of 62-99% for the diagnosis of RAS.[29,30] Results of a prospective study that compared DUS with angiography are summarized in Table 2.[31] DUS is also an excellent test for the follow-up of patients with RAS after percutaneous therapy or surgical bypass.[32,33]

 

A common practice is to schedule renal artery DUS within the first few weeks after endovascular therapy to establish baseline results, and then to repeat the study at 6 months, 12 months, and annually thereafter to look for restenosis. However, this strategy has never been tested in a clinical trial. One drawback of DUS is that its sensitivity is lower for identifying accessory renal arteries (67%) compared with main renal arteries (98%).[29] If the patient has hypertension that cannot be adequately controlled, therefore, and DUS fails to demonstrate RAS, another imaging modality might be needed to identify stenosis in an accessory renal artery.

Resistance Index. The resistance index, which is an adjunctive measure obtained during renal DUS, is the ratio of the peak systolic to end diastolic velocity within the renal parenchyma at the level of the cortical blood vessels. Resistance index is a representation of the amount of small-vessel arterial disease (i.e. nephrosclerosis) within the renal parenchyma. Besides being used to screen patients for possible RAS, the resistance index could be used to stratify patients according to how likely they are to respond to renal intervention.[34] However, data on the ability of resistance index to predict treatment response in patients with RAS are conflicting.

Radermacher and associates[34] treated 81 patients with balloon angioplasty alone, 42 patients with angioplasty and stents, and 8 patients with surgical revascularization. These authors demonstrated that an elevated resistance index (>80) was associated with a lower probability of improved blood pressure (BP) or renal function after revascularization, compared with a resistance index of less than 80 regardless of treatment strategy. This study was, however, retrospective and without prespecified end points, and the results have not been duplicated in other reports.[35,36] A prospective study of renal stent placement in 241 patients demonstrated that individuals with an elevated resistance index (>80) achieved a favorable BP response and renal functional improvement at 1 year after renal arterial intervention.[35,36] Zeller and coworkers[36] demonstrated that patients with the most abnormal resistance index values experienced the greatest magnitude of benefit. Until more information becomes available, an elevated resistance index should not be considered a contraindication to performing renal artery revascularization.[2]

CT Angiography. CTA is often used in patients who cannot be adequately imaged with DUS (Figure 2A), such as very obese patients, or patients with excessive abdominal gas. Excellent image quality with enhanced resolution can be obtained with multidetector-row CTA technology.[32,37] The advantages of CTA over MRA include higher spatial resolution, absence of flow-related phenomena that can overestimate the degree of stenosis, and the capability to visualize calcification and metallic implants, such as endovascular stents and stent grafts. The disadvantages of CTA compared with MRA and DUS are exposure to ionizing radiation and the use of potentially nephrotoxic iodinated contrast agents

 

Depending on the specific technique used, CTA has excellent sensitivity (89-100%) and specificity (82-100%) for detecting RAS.[38-41] Limited data are available on the use of CTA in detecting restenosis after renal artery stent implantation (in-stent restenosis), but this technique also seems to be a promising noninvasive method to evaluate patients after stent implantation.[42-44] CTA is not the ideal screening test for RAS in patients with renal insufficiency because of the potential nephrotoxicity of iodinated contrast agents. Patients must also be able to suspend their respiration for 15-30 s during image acquisition, since respiratory artifacts substantially degrade the image quality. CTA is well-tolerated with an open gantry and, therefore, patients' claustrophobia is not usually a limiting factor, as it is for MRA where the gantry is closed.

Magnetic Resonance Angiography. MRA, like CTA, provides excellent imaging of the abdominal vasculature and associated anatomical structures (Figure 2B). Patients must be able to hold their breath to minimize motion artifacts during image acquisition so as not to compromise the quality of the study. Compared with CTA, MRA has a sensitivity of 91-100% and a specificity of 71-100%.[45-48]

Contrast-enhanced MRA using gadolinium results in improved image quality and reduced imaging time when compared with noncontrast studies, which eliminates some of the artifacts created by the patient's movement.[49,50] A meta-analysis of 39 studies reported a sensitivity and specificity of 94% and 85%, respectively for nonenhanced studies, compared with a sensitivity and specificity of 97% and 93%, respectively for contrast-enhanced studies. MRA does not, however, have the same sensitivity and specificity in patients with fibromuscular dysplasia and is generally not a good screening test if this condition is suspected.[51]

A new technology to assess renal ischemia uses blood-oxygen-level-dependent MRI to detect changes in tissue deoxyhemoglobin. Preliminary data indicate that this technique, combined with suppression of tubular oxygen consumption, can be used to assess regional tissue oxygenation in kidneys of patients with vascular occlusive disease.[52] Further studies are warranted in this area.

In 2008, Prchal et al. published data that indicated that MRA should not be used in patients with a glomerular filtration rate (GFR) of less than 30 (ml/min)/1.73 m2 because of an increased risk of nephrogenic systemic sclerosis.[53] In addition, MRA should not be used in patients with metallic (ferromagnetic) implants, such as some mechanical heart valves, cerebral aneurysm clips, and electrically-activated implants (e.g. pacemakers, spinal-cord stimulators). Furthermore, MRA is not useful for follow-up of patients after stent implantation because of artifacts produced by the metallic stent.

Biomarkers. Renin and brain natriurietic peptide (BNP), are biomarkers of renal ischemia. All manifestations of the abnormal physiology related to RAS—renovascular hypertension, ischemic nephropathy, and cardiac destabilization (i.e. pulmonary edema)—are caused by hypoperfusion of the kidney, which leads to renin release from the juxtaglomerular cells. Measurement of renin levels is not, however, reliable in clinical practice as many medications (e.g. β-blockers, angiotensinconverting enzyme inhibitors) can stimulate or suppress renin production. In addition, patients with bilateral renal artery disease, or disease of a single functioning kidney, can have suppressed renin levels because of volume expansion.[27] BNP is a neurohormone that is released from the ventricular myocardium under conditions that cause myocardial cell stretching, such as congestive heart failure (CHF). BNP promotes diuresis, natriuresis, arterial vasodilation, and antagonizes renin.[54] In vitro data have shown that angiotensin II can directly induce synthesis and release of BNP,[55] and an animal study has indicated that BNP messenger RNA is significantly upregulated 6 h after clipping the renal artery.[55,56]

A study by Silva et al.,[57] of 27 patients with poorly controlled hypertension and RAS (≥70% stenosis), showed that BNP was elevated (median 187 pg/ml; 25.75% percentiles, 89.306 pg/ml) before stent placement and fell within 24 h of successful stent placement (median 96 pg/ml 25.75% percentiles, 61.182 pg/ml; P = 0.002). Hypertension improved in 17 of 22 patients (77%) with a baseline BNP of more than 80 pg/ml compared with none of the 5 patients with a baseline BNP of 80 pg/ml or less (P = 0.001). The findings of this intriguing study need to be confirmed in a larger cohort of patients.

Invasive Assessment

Catheter Angiography. The indications for screening angiography for RAS at the time of cardiac or peripheral angiography of other vascular beds were addressed by AHA and ACC recommendations and guidelines published in 2006.[2,58] For patients with risk factors (Box 2) or clinical evidence of RAS, aortography is given a class I recommendation for screening at the time of angiography for other clinical indications. Evidence has been published that nonselective, diagnostic screening renal angiography is safe, and is not associated with any incremental risk when performed at the time of cardiac catheterization.[16]

A visually estimated stenosis of 70% or greater is considered hemodynamically significant, and is a generally accepted indication for percutaneous intervention.[59] Unfortunately, visual estimation of the severity of stenosis has a high degree of interobserver variability and compares poorly with quantitative methods of lesion assessment (Figure 3). Renal frame count, which is analogous to Thrombolysis In Myocardial Infarction frame count in coronary angiography, is another angiographic tool that can be used to assess the adequacy of renal blood flow. Mulumudi and White[60] compared renal frame counts in patients with fibromuscular dysplasia and a group of individuals with normal renal arteries. Renal frame count was defined as the number of cine frames required for contrast to reach the smallest visible distal branch of the renal parenchyma. Compared with normal individuals, mean renal frame count for the arteries of patients with fibromuscular dysplasia was significantly increased (26.9 ± 9.9 versus 20.4 ± 3.0, 95% CI 21.4-32.4, P = 0.0001).[60] Renal frame count takes into account macrovascular blood flow in the main renal artery and its segmental branches, as well as micro vascular resistance in the cortex and medulla, and is a potentially valuable angiographic tool for assessing renal blood flow.

 

Translesional Pressure Gradient. The relief of hemodynamic obstruction (translesional pressure gradient) without injury to the renal parenchyma, rather than the cosmetic improvement of angiographic stenosis, is the ultimate goal of RAS reperfusion (Figure 4). An expert consensus panel of the AHA recommended that a peak systolic gradient of at least 20 mmHg, or a mean pressure gradient of 10 mmHg, be used to identify candidate lesions for revascularization in symptomatic patients with RAS.[59] The value of absolute 'threshold' pressure gradients has been questioned. A 10 mmHg translesional pressure gradient might not be as physiologically important when systolic BP is 200 mmHg, as when systolic BP is 140 mmHg.

 

Translesional pressure gradients can be unreliable indicators of borderline lesions because the gradient is dependent upon the diameter of the catheter placed across the lesions, the aortic pressure, the degree of stenosis, the distal vascular bed, and the renal venous pressure. The catheter itself can introduce an artificial gradient.[61] The physiological limitation of translesional pressure gradients needs to be recognized—that is, the principle that organ perfusion is related to the perfusion pressure distal to the stenosis, but not to the pressure gradient itself.[62] Translesional pressure gradients can be altered by factors that affect blood flow, such as cardiac output, systemic BP, and the vasodilatory state of the renal microvasculature.

Renin secretion from a hypoperfused kidney is a key element in the development of renovascular hypertension. De Bruyne and colleagues[63] investigated the concept of a 'threshold' translesional pressure gradient, and their study quantified the degree of functional stenosis required to trigger renin production. A good correlation existed between the ratio of systolic BP in the aorta (Pa) to the systolic pressure in the renal artery distal to the stenosis (Pd), and absolute pressure gradients. The authors also demonstrated no significant increase in renal vein renin levels for a Pd /Pa gradient greater than 0.9, which identified a group of patients who are unlikely to benefit clinically from renal revascularization.

Fractional Flow Reserve. Another method to determine the severity of angiographic RAS is to quantify the fractional flow reserve (FFR). The FFR is a measure of pressure in the coronary circulation, which is based on the principle that flow across a conduit artery is proportional to pressure across the vascular bed and is inversely proportional to the resistance of the vascular bed. Under conditions of maximum hyperemia (i.e. maximum vaso dilation), the flow through the conduit artery is maximal, while the resistance of the vascular bed is at a minimum and constant. Any reduction in flow under these conditions is caused by the stenosis and is proportional to the ratio of pressure distal to the stenosis and the pressure proximal to the stenosis. FFR is measured after induction of maximum hyperemia (e.g. after intrarenal administration of intrarenal papa verine) using a non obstructive wire with a pressure transducer located at its distal segment.

In a study by Mitchell et al.,[64] renal FFR was measured after renal stent placement in 17 patients with refractory hypertension and moderate to severe (50.90% stenosis), unilateral RAS. Ten patients had normal baseline renal FFR (≥0.80), whereas an abnormal baseline renal FFR (<0.80) was recorded in seven patients. Preprocedure BP, severity of RAS, the number of antihypertensive medications being taken, and estimated GFR did not differ between the two groups. At 3 months after intervention, 86% of patients with an abnormal renal FFR experienced improvement in their BP, compared with only 30% of those with normal renal FFR (P = 0.04). No differences were seen in the baseline systolic, mean, or hyperemic translesional pressure gradients among patients whose BP improved and those in whom it did not. Neither systolic, mean, or hyperemic translesional pressure gradients, nor the severity of angiographic stenosis, were predictive of BP improvement.[64]

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Treatment Of Renal Artery Stenosis

Revascularization

Control of BP with medical therapy does not prevent progression of RAS;[65,66] however, the effect of lipid-lowering medications (i.e. statins) is not known. A randomized trial of optimum medical therapy compared with balloon angioplasty for the treatment of renovascular hypertension found that 16% of medically treated patients experienced renal artery occlusion within 1 year, compared to none of the patients treated with angioplasty.[67] Percutaneous, catheter-based therapy has replaced surgical renal revascularization for atherosclerotic RAS because of the increased morbidity and mortality associated with surgery.[68-71]

Three randomized trials have compared renal artery balloon angioplasty with medical therapy for the treatment of renovascular hyper tension. The findings of these studies support the superiority of catheter-based therapy. Plouin and colleagues[72] found that BP reduction was greater among 23 patients who underwent angioplasty than among 26 patients who received medical therapy (systolic BP 14 ± 20 mmHg versus 7 ± 23 mmHg, P = 0.24; diastolic BP 8 ± 11 mmHg versus 1 ± 12, P = 0.04). A study by Webster et al.[73] of 55 patients with bilateral RAS also demonstrated a significant improvement in BP among those treated with angioplasty versus patients who received medical therapy. In a third study, 106 patients were randomly assigned to balloon angioplasty or medical therapy.[67] At 3 months, 22 of the 50 medically treated patients (44%) had failed to respond adequately to therapy and required angioplasty, which demonstrated the superiority of percutaneous intervention. In addition, the results of a controlled trial demonstrated a statistically significant benefit for angioplasty with stenting compared with medical therapy for reduction in systolic BP (21.9 ± 10.5 versus 10.9 ± 8.5, P <0.05) and diastolic BP (10.4 ± 6.3 versus 7.7 ± 4.1, P <0.05).[74] Finally, two metaanalyses concluded that renal angioplasty was superior to medical therapy for BP control and for improving renal function.[75,76]

Stenting Versus Balloon Angioplasty

Balloon angioplasty is much less effective than stent placement for treating atherosclerotic aorto-ostial plaque (Figure 5). Renal stents have been shown to lower the translesional pressure gradient significantly when compared with balloon dilation alone.[77] The superiority of renal stents over balloon angioplasty alone has also been confirmed in a randomized trial and in two meta-analyses (Figure 6).[78-80] This evidence led to a class I guideline recommendation by the ACC and AHA for primary stent placement in atherosclerotic RAS.[2] Analogous to findings from coronary artery stent trials, renal stent patency correlates with 'acute gain' and larger stent minimum lumen diameters.[81,82] Reported restenosis rates for renal stents range from 11% to 14%.[78,83-86] Two studies reported 5-year renal stent primary patency rates approaching 80%, and secondary patency rates greater than 90%.[83,84]

 

Selection of Patients

Optimum selection of patients for renal revascularization is more complex than a visual estimation of stenosis, or a measurement of a translesional pressure gradient. Patients with RAS have multifactoral reasons for hypertension and renal insufficiency that might or might not improve as renal blood flow improves. Perhaps the most common reason that patients fail to improve after renal revascularization is over estimation of the severity of RAS by angiography. The ostial segment of the renal artery has a complex three-dimensional geometry that can be very difficult to appreciate with two-dimensional angiographic imaging. Angioplasty or stent placement in mildly narrowed renal arteries would not be expected to be of much clinical benefit, and could be the reason why no more than 60-70% of patients with hypertension improve after renal revascularization (Figure 7).[80] Many patients have had essential (primary) hypertension for years and then develop atherosclerotic RAS late in life. The presence of anatomic RAS does not establish that RAS is the cause of a patient's hypertension or renal failure.

Renovascular Hypertension

Despite a technical success rate exceeding 95% for renal artery stent placement, wide variation remains in the reported rates of hyper tension improvement with this technique. At least some of this outcome variability is attributable to the lack of standard reporting criteria,[59] but poor selection of patients could be an even more important factor.[63,64] Although the majority of patients with atherosclerotic RAS and hyper tension will experience improved BP control, or require fewer medications (or both), very few patients will be cured of hypertension (Figure 7).[79,83,84,87]

Patients with the highest systolic BPs experience the greatest decreases in systolic BP after renal artery stenting, but BP improvement does not correlate with patient age, sex, ethnicity, severity of stenosis, number of vessels treated, baseline diastolic BP, or baseline serum creatinine level.[88] Bilateral RAS (odds ratio 4.6, P = 0.009) and mean arterial pressure greater than 110 mmHg (odds ratio 2.9, P = 0.003) are, however, associated with improvement in BP after renal artery stent placement.[86] Studies that compared the results of renal artery stenting in elderly (≥75 years) versus younger patients, or in women versus men, have failed to show any difference in response to renal stent placement.[89,90]

Ischemic Nephropathy

Two small trials have indicated that renal artery stent placement improves or stabilizes renal function in patients with atherosclerotic ischemic nephropathy. In the first study, 32 patients with unexplained renal insufficiency and hemodynamically significant RAS had a fourfold reduction in the rate of progression of renal insufficiency after renal artery stent placement.[91] The majority of these patients had bilateral stenosis or disease of a single functioning kidney, although unilateral disease was present in seven patients. Another study confirmed improvement or stabilization of renal function in patients who underwent successful renal artery stent placement for bilateral stenosis or disease of a single functioning kidney (≥70% stenosis).[92] One of the best predictors of improved renal function after renal revascularization is the rate of decline in renal function. The more rapid the onset and severity of the renal insufficiency, the more likely revascularization is to be of benefit (Figure 8).[93]

A meta-analysis of 10 studies showed that serum creatinine levels improve in about 25% of patients who undergo renal artery stent placement, remain the same in about half of patients, and worsen in the remainder.[79] The worsening in serum creatinine level is likely to be caused by either contrast nephropathy or atheroembolization. Atheroembolic debris retrieval has been described in several series, and atheroembolization is apparently quite common with renal stent placement.[94-96] Although the surrogate end point of successful emboli retrieval has been documented, clinical end points, such as the safety and efficacy of embolic protection devices, remain to be demonstrated.

Cardiac Disturbance Syndromes

Cardiac disturbance syndromes attributable to RAS include exacerbations of coronary ischemia and CHF, which is caused by peripheral arterial vasoconstriction, volume overload, or both. Renovascular disease can also complicate the management of patients with heart failure by preventing the use of an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker.

The importance of renal artery stent placement in the treatment of cardiac disturbance has been described in a series of patients who presented with either CHF or an acute coronary syndrome.[97] Successful renal stent placement resulted in a significant decrease in BP and control of symptoms in 42 of 48 patients (88%). Some patients underwent both coronary and renal intervention, while others had only renal artery stent placement because coronary lesions were unsuitable for revascularization. Immediate treatment effects and those at 8 months, as assessed by Canadian Cardiovascular Society angina class and NYHA functional status, did not differ between the combined coronary and renal revascularization group and the renal-stent-only group, which indicated that renal revascularization was the most beneficial intervention.[97]

In another study, 39 patients underwent renal artery stent implantation for control of CHF,[98] 18 of whom (46%) had bilateral RAS, and the other 21 (54%) had stenosis of a solitary functioning kidney. Renal artery stent implantation was technically successful in all patients. Improvements in BP and renal function were recorded in 72% and 51% of patients, respectively, and renal function was stable in 26% of patients. The mean number of hospitalizations for CHF fell from 2.4 ± 1.4 before intervention to 0.3 ± 0.7 after renal stenting (P <0.001). During follow-up (mean 21.3 months) 77% of patients had no further hospitalizations. Improvements in BP and renal function after revascularization occur because of a reduction in stimulation of the renin-angiotensin system. In addition, successful angioplasty allows patients who could not otherwise be treated with angiotensinconverting enzyme inhibitors or angiotensin II receptor blockers without exacerbating renal failure, to take these beneficial medications.

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Safety Issues

Diagnosis

Catheter-based angiography can lead to complications associated with vascular access or catheter trauma. In addition, systemic and renal toxicity can be caused by iodinated contrast agents. The incidence of major complications associated with peripheral vascular angiography ranges from 1.9% to 2.9% (Table 3).[99] Atheroembolism, vessel dissection, and arterial perforation caused by catheterization of the renal artery are rare (<1%), but often devastating, events. Anaphylactic reactions to contrast media occur in less than 3% of patients, and less than 1% require hospitalization.[100] The risk of contrast-induced nephropathy is increased in patients with baseline chronic renal insufficiency, diabetes mellitus, multiple myeloma, and those who are receiving other nephrotoxic drugs such as aminoglycosides. Patients who develop contrast-induced nephropathy have a poor prognosis.[101] Optimum prevention requires vigorous hydration and the use of as little contrast as possible. Other adjunctive strategies, including pretreatment with N-acetylcysteine, intravenous bicarbonate, or both, can be considered, although their effectiveness remains unclear.[102]

Treatment

Embolic Protection Devices. Embolic protection devices were developed for clinical use in saphenous-vein coronary bypass grafts and for cerebral protection during carotid stenting. Percutaneous embolic protection devices can be divided into three categories: filters, distal occlusion balloons with aspiration of debris, and proximal occlusion balloons with reversal of flow. The aorto-ostial nature of most RAS makes proximal occlusion devices unsuitable. Distal occlusion balloons and filters are, therefore, the most common devices that have been used off-label for renal protection during stent placement.

Renal atheroembolization has been documented by renal biopsies and by DUS in patients undergoing surgical revascularization of RAS.[103,104] Cholesterol crystals and plaque debris lodge in small capillaries and distal arterioles where they cause a local inflammatory response that results in intimal hyper proliferation and subsequent vessel occlusion. Renal dysfunction is a common result. Kawarda and associates[103] demonstrated microembolic signals (athero matous embolization) detected by DUS at the time of renal artery stenting in all 13 patients who were examined. In another study, approximately a third of a group of 44 patients who underwent surgical therapy for atherosclerotic RAS had biopsyproven atheroembolization.[105] Atheroembolism was associated with an increase in surgical morbidity and a dramatic reduction in 5-year survival compared with patients who had no evidence on biopsy of renal athero embolization (54% versus 85%, P = 0.011).

A distal occlusion balloon (Guardwire®, Percusurge, Inc., Sunnyvale, CA) embolic protection device used off-label for renal protection during stent deployment has been described in several studies.[96,106,107] Total angiographic success with successful stent placement was accomplished, and visible debris was aspirated from every renal artery. At 6 months after the procedure, renal function had not deteriorated in any of the patients, and had actually improved in five individuals with baseline renal insufficiency. Filter embolic protection devices have been used in several small series.[108,109] In one study, visible emboli were captured in 65% of the filters.[106] No patients suffered acute deterioration in renal function and 95% of patients experienced stabilization or improvement in renal function.[106]

The use of intravenous glycoprotein IIb/IIIa platelet receptor inhibitors could have a role in improving outcomes after renal stent placement, by the same mechanism that they improve outcomes after coronary intervention.[110] Embolic protection devices and glycoprotein IIb/IIIa inhibitors used together could protect the renal microcirculation from atheroembolization and platelet aggregation, which seems to be ubiquitous. In a study of 100 patients, the use of an embolic protection device alone, a glycoprotein IIb/IIIa inhibitor (abciximab) alone, an embolic protection device plus a glycoprotein IIb/IIIa inhibitor, and a control (placebo) were compared.[111] Patients in the placebo, embolicprotection-device-alone, and glycoprotein IIb/IIIa inhibitor groups demonstrated a decline in GFR (P <0.05), but GFR improved among patients who received both an embolic protection device and a IIb/IIIa glycoprotein inhibitor (Figure 9). An interaction was observed between abciximab and embolic protection (P <0.05) that favored combination treatment.

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Conclusions

Catheter-based therapy for symptomatic (hypertension, ischemic nephropathy, or cardiac destabilization syndromes), hemodynamically significant, atherosclerotic RAS is the preferred method of revascularization. Stent placement is favored over balloon angioplasty and carries a class I recommendation for treatment of atherosclerotic RAS.[2] Discordance between the high (>95%) procedural success and the moderate (60-70%) clinical response after stenting is likely to be a result of three factors: poor selection of patients, poor discrimination of lesion severity by angiography, and the concomitant presence of parencyhmal renal disease. Preliminary data indicate that the use of physiologic lesion assessment with pressure gradients, renal FFR, and biomarkers (e.g. BNP), could enhance lesion selection and result in improved clinical response rates.[57,64] Further studies in large series of patients are needed to establish the clinical role of these strategies.

The development of new technologies to improve the safety and efficacy of renal intervention further are on the horizon. Several investigators have demonstrated the feasibility and safety of embolic protection, although prospective trials to determine the efficacy of these devices in preservation of renal function have not yet been performed. The current longterm patency rates for renal stenting are excellent, with restenosis rates approaching 10% and 5-year secondary patency rates exceeding 90%. Given the importance of improving vessel patency acutely, and of preventing late lumen loss, a potential role for drug-eluting stents exists in patients at high risk for restenosis, those with small (<4.5 mm diameter) reference vessels, and those with in-stent restenosis.[81,82,112

Diagnosis and Management of Atherosclerotic Renal Artery Stenosis: Improving Patient Selection and Outcomes

Please answer the test questions below. Some activities require you to meet a certain passing score to earn credit.

Questions answered incorrectly will be highlighted.

1. Which of the following statements about the epidemiology and etiology of renal artery stenosis (RAS) is most accurate?

Among older adults, RAS is more common in men than in women

Blacks have higher rates of RAS compared with whites

RAS is not a prominent cause of secondary hypertension

Fibromuscular dysplasia is the most common cause of RAS, even among older adults

2. Which of the following imaging tests is the best choice to screen for RAS?

Magnetic resonance angiography (MRA)

Computed tomography angiography (CTA)

Captopril-stimulation renal flow scan

Renal duplex ultrasonography

Renal artery angiography

3. Which of the following statements about treatment of RAS is most accurate?

Optimum medical therapy is as effective as balloon angioplasty for renovascular hypertension

Renal artery balloon angioplasty is as effective as renal stent placement for the treatment of atherosclerotic aorto-ostial plaque

Only 60% to 70% of patients with hypertension improve after renal revascularization

Blood pressure improvement after renal artery stenting correlates with the baseline severity of stenosis

4. All of the following results have been associated with renal artery stenting, except:

Improvement or stabilization of renal function

Reduction in hospitalizations for congestive heart failure

Procedural success rates exceeding 95%

Restenosis rates of 50% with renal stents

Below are all the test questions with an explanation of the correct answer. Questions answered incorrectly will be highlighted.

Which of the following statements about the epidemiology and etiology of renal artery stenosis (RAS) is most accurate?

Answer: Among older adults, RAS is more common in men than in women
In a study of individuals in a Medicare population, RAS was present in almost twice as many men as women. However, no differences were noted in the prevalence of RAS between white and blacks individuals. In the general hypertensive population, RAS is the most common (2%-5%) secondary cause of hypertension. In the adult population, RAS is predominantly the result of atherosclerosis, not fibromuscular dysplasia.

Which of the following imaging tests is the best choice to screen for RAS?

Answer: Renal duplex ultrasonography
Renal duplex ultrasonography can be performed without altering the patient's antihypertensive regimen, and does not require administration of potentially toxic contrast agents, making it the imaging procedure of choice. MRA and CTA should be used for patients who cannot be adequately assessed with ultrasonography, and the captopril-stimulation renal flow scan is a second-line imaging test for RAS. When possible, noninvasive direct imaging tests are preferable to invasive studies, such as renal artery angiography.

Which of the following statements about treatment of RAS is most accurate?

Answer: Only 60% to 70% of patients with hypertension improve after renal revascularization
Trials comparing renal artery balloon angioplasty with medical therapy for the treatment of renovascular hypertension support the superiority of catheter-based therapy. However, renal balloon angioplasty is much less effective than stent placement for treating atherosclerotic aorto-ostial plaque. Patients with the highest systolic blood pressure experience the greatest reductions in systolic blood pressure after renal artery stenting, but blood pressure improvement does not correlate with patient age, sex, ethnicity, severity of stenosis, number of vessels treated, baseline diastolic blood pressure, or baseline serum creatinine level. Despite a high (> 95%) procedural success rate, only 60% to 70% of patients with hypertension improve after renal revascularization, which is likely to be a result of poor patient selection or poor discrimination of lesion severity.

All of the following results have been associated with renal artery stenting, except:

Answer: Restenosis rates of 50% with renal stents
Renal artery stent placement is associated with a technical success rate that exceeds 95% and with reportedly low rates of restenosis ranging from 11% to 14%. Trials have shown that renal artery stent placement improves or stabilizes renal function and has also been shown to significantly reduce the rate of hospitalizations for congestive heart failure.

Sucos concentrados têm alto teor de minerais

O suco concentrado de frutas nacionais pode ser uma opção prática para uma alimentação mais rica em nutrientes. A troca de um alimento natural por outro industrializado não deve ser estimulada, mas os sucos concentrados têm seu lado positivo, pois contêm quantidade significativa de alguns minerais essenciais ao organismo humano. É o que sugere um estudo coordenado por Lucia M. Valente Soares, da Faculdade de Engenharia de Alimentos da Universidade Estadual de Campinas (Unicamp).




“Foram analisados sucos de abacaxi (3 marcas), caju (5 marcas), goiaba (3 marcas), manga (2 marcas), maracujá (5 marcas) e pitanga (1 marca). Todas as marcas eram de circulação nacional”, explicam Lucia e sua equipe em artigo publicado na revista Ciência e Tecnologia de Alimentos, na edição de abril-junho de 2004.


Segundo o artigo, todos os sucos analisados são uma boa fonte de potássio. Preparado de acordo com a diluição indicada no rótulo, um copo de 300 mililitros dos sucos fornece de 170% a 930% da ingestão diária recomendada (RDA) de potássio para uma criança.


Além disso, 300ml dos sucos de abacaxi e acerola já diluídos podem fornecer para uma criança 6% e 12% da RDA de ferro, respectivamente. No caso dos sucos de abacaxi, manga, goiaba e acerola, esse mesmo volume de bebida já diluída contém, respectivamente, 38%, 14%, 8% e 7% da RDA de manganês para uma criança. O suco de abacaxi pode ainda contribuir para a dieta infantil com 9% da RDA de magnésio.


Lucia e sua equipe lembram que, sobretudo para o magnésio e o ferro, a quantidade de minerais presente nos sucos também contribui para satisfazer as necessidades nutricionais dos adultos. No entanto, os sucos não apresentam uma composição nutricional constante, devido inclusive à variação natural no teor de minerais das frutas.


Agência Notisa :::. fonte: www.sbh.org.br


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Redução pequena de peso produz grande proteção contra hipertensão

De acordo com estudos realizados recentemente pela Drª L.L.Moore,da Boston University School of Medicine,em Massachusetts,EUA ,sugerem que a redução pequena de peso, de 0,5 kg por ano pode diminuir ,substancialmente o risco, a longo prazo,do desenvolvimento de hipertensão,se essa mesma perda de peso puder ser mantida.

Esse resultado foi obtido através de dois grupos de estudos : o 1º, com 922 homens e mulheres acima do peso com idades de 30 a 51 anos, o 2º ,com 901 homens e mulheres acima do peso com idades de 50 a 65 anos .

Durante 4 anos, separadamente, esse grupos foram analisados tomando como base o IMC de 25 ou mais, e a definição de hipertensão foi de 160mmHg/95 mmHg.

Os melhores resultados ,independente da idade, foram para as pessoas que estavam mais acima do peso, obtendo uma redução de 40% até 50% do risco de desenvolver hipertensão.

Um outro grupo que tinha um IMC de 27 em condições basais,obteveuma redução de 25% a 30% do risco.

Diante da apresentação dos trabalhos realizados pela Drª Moore, o presidente da AHA, Dr.L. Smaha que coordenava uma mesa sobre obesidade , disse: " Para mim mesmo, como clínico, isso significa que posso afirmar a meus pacientes que, mesmo se perderem apenas um pouco de peso, haverá um impacto positivo."

Meditação reduz aterosclerose em pacientes hipertensos

Um estudo publicado no Stroke relata que é possível reduzir o estresse usando meditação transcendental associado a uma redução da aterosclerose carotídea.Os pesquisadores do College of Maharishi Vedic Medicine,em Fairfield,EUA, liderados

pela Dra. A Castillo-Richmond, estudaram 138 pessoas afro-americanos com pressão arterial normal alta ou com hipertensão estágio 1 ou 2.Dois grupos foram formados aleatóriamente para um programa de meditação ou um programa de educação sobre fatores de risco de doença cardiovascular.

Durante 6 a 9 meses,o grupo de meditação meditava durante 20 minutos ,duas vezes ao dia,e o outro realizava exercícios domiciliares pelo mesmo tempo a cada dia.

Após o término do estudo, a EIM média declinou em 0,098mm no grupo da meditação, e aumentou 0,054 no grupo de educação para a saúde.Estima-se que o declínio no grupo da meditação indique uma redução de 11 % no risco de infarto agudo do miocárdio e uma queda de 7,7 % a 15 % no risco de acidente vascular cerebral.

Para os pesquisadores " os resultados tem potencialmente implicações importantes para a prevenção e o tratamento de aterosclerose e suas conseqüências clínicas e epidemiológicas",tanto que a Dra.Castillo está tentando com a equipe reproduzir os achados em um grupo maior de participantes.

Inibição da ECA melhora relaxamento endotélio-dependente na vasculatura renal

" A inibição da ECA é benéfica não somente em baixar a pressão arterial ,mas também em melhorar a disfunção endotelial renal em pacientes com hipertensão essencial" é o que relatam os autores do estudo chefiado pelo Dr.Y.Higashi,da Escola de Medicina da Universidade de Hiroshima, Japão e publicado recentemente no Hypertension.

Os pesquisadores compararam os efeitos do inibidor da ECA
(enzima conversora da angiotensina)imidapril e o antagonista do cálcio amlodipina sobre a função endotelial renal em pacientes com hipertensão essencial sem aterosclerose.

Um grupo de 27 pessoas foi designado para receber um em dois tratamentos por 12 semanas.A resistência vascular renal e a concentração de nitrito/nitrato em resposta a L-arginina foram medidas no começo e no final do estudo.

Após três meses de tratamento ,alguns resultados foram semelhantes para os dois grupos,como a diminuição da pressão arterial e o aumento do fluxo plasmático renal.Contrastando,o relaxamento renovascular induzido por L-arginina aumentou com imidapril, mas não com a amlodipina.O mesmo ocorreu com a excreção urinária da nitrito/nitrato que aumentou com o uso do inibidor da ECA, mas não alterou com o antagonista do cálcio.Baseado nesses resultados os pesquisadores concluíram que inibir a ECA melhora o comprometimento renovascular dependente do endotélio em pacientes com hipertensão essencial por aumento da produção de óxido nítrico.

E que a incapacidade da amlodipina em alterar a função renal sugere para a equipe do Dr.Higashi que a redução da pressão arterial pelo tratamento de um antagonista do cálcio " não desempenhe um grande papel na potencialização dos efeitos mediados por L-arginina/óxido nítrico."

Exercícios moderados para mulheres grávidas com risco de hipertensão

Foi na University of Michigan School of Nursing ,EUA, que a Dra. S.Yeo e colegas estudaram prospectivamente os efeitos dos exercícios sobre a pressão arterial em 16 mulheres grávidas, com história de hipertensão leve,distúrbios hipertensivos gestacionais ou antecedentes familiares de hipertensão.

Após 10 semanas ,constatou-se que a pressão sistólica não sofreu alteração significativa em nenhum dos dois grupos.Porém, o grupo dos exercícios, a pressão diastólica diminuiu 3,5 mmHg,e no grupo controle, a pressão diastólica aumentou 1,1 mmHg.

Segundo a Dra.Yeo,este resultado não estava associado à alteração do peso corporal, já que esse aumento se manifestou em ambos os grupos durante o estudo."Foram as caminhadas,acreditamos,a única causa da diminuição da pressão arterial diastólica.A hipertensão algumas vezes leva à pré-eclâmpsia, e esta doença é a principal causa de óbito materno.Também pode ter um efeito negativo sobre o bebê" e levar à necessidade de parto prematuro, destacou a Dra.Yeo.

Para os investigadores, estes achados mostram que um programa de exercícios moderados para mulheres grávidas com alto risco de hipertensão é eficaz em reduzir a pressão arterial diastólica, isso quer dizer que essas mulheres podem exercitar-se seguramente se tiverem supervisão apropriada.

O estudo foi publicado recentemente no Journal of Reproductive Medicine.

Estratificação de risco importante no tratamento anti-hipertensivo

Os benefícios absolutos do tratamento anti-hipertensivo dependem não apenas da pressão arterial, mas também, da presença ou ausência de outros fatores,segundo os resultados de um estudo a longo prazo chefiado pelo Dr. He,da Tulane University School of Public Health and Tropical Medicine, em New Orleans,EUA e publicado recentemente no Hypertension.

Foram 10 anos trabalhando com 12.300 pacientes a fim de determinar os benefícios absolutos obtidos em reduzir a pressão arterial sistólica em 12 mmHg,seguindo o sistema de estratificação de risco recomendado pelo sexto relato da Joint National Committee on Prevention,Detection,Evaluation and Tratment oh High Blood Pressure(JNC VI)que deve incluir a pressão arterial de nível médio do paciente,bem como a presença ou ausência de órgãos-alvo e outros fatores de risco.

Os participantes foram divididos em 3 categorias de pressão arterial(normal alta,hipertensão estágio 1 e estágio 2 ou 3) e em 3 grupos de risco: A, pacientes que não apresentavam doença cardiovascular,lesão de órgãos-alvo ou outros fatores de risco para doença cardiovascular ; B: não tinham doença cardiovascular, lesão de órgãos-alvo ou diabetes, mas apresentavam ,pelo menos, um outro fator de risco maior ; C: pacientes com diabetes mellitus,doença cardiovascular clinicamente manifesta, e lesão de órgãos-alvo.

De acordo com os pesquisadores " o número necessário para tratar a fim de prevenir um evento cardiovascular/óbito ou mortalidade total foi reduzido com o aumento dos níveis da pressão arterial basal em cada um dos estratos de risco".Eles ainda sugerem que os clínicos devam basear as decisões referentes ao início do tratamento anti-hipertensivo na pressão arterial,bem como no risco absoluto dos pacientes individuais,sendo assim,acredita a equipe do Dr.He que visar a população de alto risco melhorará o custo-benefício dos programas anti-hipertensivos em comunidades.

Cirurgia gástrica no controle de hipertensão em obesos

Acentuada redução de peso após gastroplastia com banda vertical ajuda a controlar a pressão arterial(PA) em hipertensos com obesidade mórbida,de acordo com investigadores de Israel.Os achados foram publicados no American Journal of Hypertension.

Chefiado pelo Dr.I.Bem-Dov, investigadores do Centro MédicoChaim Sheba, em Tel-Hashomer, mediram a pressão arterial em repouso e durante teste ergométrico em 19 pacientes com obesidade mórbida, com 41 anos de idade,antes de gastroplastia e novamente após a perda de peso.

Em média, o peso caiu de 118 kg antes da cirurgia para 85 kg depois da cirurgia,mantendo esta perda 13 meses depois da restrição gástrica.

Segundo os investigadores, " dos 19 participantes que completaram o estudo,13 eram hipertensos antes da cirurgia ",e neste grupo, a pressão arterial em repouso caiu de 133/87 mmHg antes da cirurgia para 115/77 mmHg depois da cirurgia.A pressão arterial em exercício máximo também declinou significativamente de um máximo pré-cirurgia de 181/98 mmHg para 162/83 mm Hg depois da cirurgia.

Dentro do grupo que completou o estudo, 6 pacientes eram normotensos antes da cirurgia e os níveis da pressão arterial em repouso caíram apenas 3/6 mmHg.

Para o Dr. Ben-Dov " é importante direcionar o tratamento para baixar tanto a PA em exercício como em repouso, pois baixar apenas a PA em repouso não significa que o efeito persista durante a atividade",e acrescenta "diferentemente da restrição na dieta, a redução de peso que vem após a gastroplastia é substancial e geralmente se mantém por um período mais longo,portanto, este procedimento deve ser considerado uma opção no tratamento de pacientes hipertensos com obesidade mórbida cuja PA não esteja bem controlada com anti-hipertensivos convencionais e que não consigam perder peso com uma dieta hipocalórica."



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