Atherosclerotic renal artery disease management update

In the case of atherosclerotic renal artery disease, the best conclusive results lie principally not in the degree of the stenosis but rather in the degree the renal parenchymal disease beyond the stenosis itself. These determining factors involve the controlling of the patients blood pressure, the improvement in the renal function and the beneficial results to the cardiovascular system. Besides the indispensable medical treatment, a revascularisation by angioplasty may be indicated. This procedure with or without vascular stent often allows satisfactory angiographic results. A treatment by surgical revascularisation is only recommended in the case of extensive atherosclerotic lesions of the aorta, complex lesions of the latter or an abdominal aortic aneurism. Although the frequency of restenosis of angioplasty with stent remains extremely low, the risk of cholesterol emboli due to the diffuse atherosclerotic lesions of the abdominal aorta, must be considered at the time of each aortic catheterization. The therapeutic approach of atherosclerotic renal artery disease must be dictated by the whole cardiovascular risk factors and by the threat of target organs. The control of the blood pressure and the maintenance of the renal function must be integrated in the decisional algorithm as well as the possible risks in carrying out an eventual revascularisation procedure. Finally, the renal angioplasty should in numerous situations be integrated in the overall assumption of responsibility of the atherosclerotic vascular diseases, and should be part of the medical treatment. Several questions still do exist; at what moment an atherosclerotic renal artery stenosis should and e considered critical, and which procedure should be considered for which patient? The purpose of this review is to propose a decisional tool for individualized treatments in the light of results from randomized and controlled studies.     

Evidence-based medicine in renal artery stenting

Atherosclerotic renovascular disease is an increasingly recognized cause of severe hypertension and declining kidney function. Patients with atherosclerotic renovascular disease have been demonstrated to have an increased risk of adverse cardiovascular events. Over the course of the last two decades renal artery revascularization for treatment of atherosclerotic renal artery stenosis (RAS) has gained great increase via percutaneous techniques. However the efficacy of contemporary revascularization therapies in the treatment of renal artery stenosis is unproven and controversial. The indication for renal artery stenting is widely questioned due to a not yet proven benefit of renal revascularization compared to best medical therapy. Many authors question the efficacy of percutaneous renal revascularization on clinical outcome parameters, such as preservation of renal function and blood pressure control. None of the so far published randomized controlled trials could prove a beneficial outcome of RAS revascularization compared with medical management. Currently accepted indications for revascularization are significant RAS with progressive or acute deterioration of renal function and/or severe uncontrollable hypertension, renal function decline with the use of agents blocking the renin-angiotensin system and recurrent flash pulmonary edema. The key point for success is the correct selection of the patient. This article summarizes the background and the limitations of the so far published and still ongoing controlled trials.     

Atherosclerotic process, renovascular disease and outcomes from bench to bedside

PURPOSE OF REVIEW: Atherosclerotic renal artery stenosis has become an important cause of secondary hypertension and renal dysfunction in the aging population. Its presence increases cardiovascular morbidity and mortality independent of other atherosclerotic risk factors. Therefore, novel renoprotective strategies are needed to decrease the impact of this disease. RECENT FINDINGS: Although medical therapy can be effective in patients with atherosclerotic renal artery stenosis and mild renal dysfunction, revascularization is desirable for patients with target-organ injury. Technical developments (such as drug-eluting or low-profile stents and distal protection devices) have increased the safety and effectiveness of renal revascularization, but in a significant proportion of patients renal function is not fully restored. Recent experimental evidence suggests that atherosclerotic renal artery stenosis is associated with the activation of intrarenal fibrogenic and inflammatory pathways, oxidative stress, and microvascular remodeling, and blocking these mechanisms can improve renal hemodynamics and function. SUMMARY: Despite significant advances in revascularization techniques, it remains unclear why the kidney affected by atherosclerotic renal artery stenosis often does not improve or even progressively deteriorates. In addition to the restoration of blood flow, targeted interventions to attenuate injurious intrarenal mechanisms should probably become part of a comprehensive management plan to preserve the ischemic kidney.     

Hyperfibrinogenemia is an independent risk factor for atherosclerotic renal artery stenosis

It is important to identify patients at risk for atherosclerotic renal artery stenosis because renal artery stenosis is a progressive disease and a potentially correctable problem. To determine the risk factors for atherosclerotic renal artery stenosis, we performed renal arteriography at the time of cardiac catheterization in 270 patients (M:F, 193:77, mean age: 59 years) with clinical ischemic heart disease. Before the procedure, demographic data, medical history, physical findings and laboratory data were obtained. The degree of coronary artery stenosis and renal artery stenosis was quantified with automatic edge detection technique. Significant renal artery stenosis, defined as a narrowing of the diameter by more than 50%, was identified in 28 (10%) patients. Three patients (1%) had bilateral disease. Significant coronary artery disease, defined as a narrowing of the diameter by more than 50%, was present in 231 patients (85%). By univariate logistic regression analysis, older age (68 +/- 8 vs. 58 +/- 10 years), the presence of hypertension (61% vs. 38%), the extent of coronary artery disease, a high fibrinogen level (391 +/- 93 mg/dl vs. 335 +/- 109 mg/dl), a low albumin level (3.9 +/- 0.4 g/dl vs. 4.1 +/- 0.4 g/dl), and a low hemoglobin level (12.5 +/- 1.6 g/dl vs. 13.5 +/- 1.6 g/dl) were associated with the presence of renal artery stenosis (p < 0.05). Serum lipids, lipoprotein(a), creatinine, sex, smoking, or diabetes were not associated. By multivariate logistic regression analysis, older age (OR: 2.43 analyzed by 10 years increment, p = 0.0001), the presence of hypertension (OR: 2.68, p = 0.039) and a higher fibrinogen level (OR: 1.63 analyzed by 100 mg/dl increment, p = 0. 038) were significant risk factors of renal artery stenosis. Fibrinogen level was negatively correlated with albumin level (r = -0.18, p = 0.004). These results suggest that hyperfibrinogenemia as well as old age and hypertension are independent risk factors for atherosclerotic renal artery stenosis. Copyright Copyright 1999 S. Karger AG, Basel     

The natural history of atherosclerotic and fibrous renal artery disease

Summary Individuals with atherosclerotic or fibrous renal artery disease may develop renovascular hypertension and/or renal dysfunction. Traditionally, the motivation for identifying patients with renal artery stenosis was the treatment of renovascular hypertension. However, recent interest has centered on the investigation of patients suspected of having renal artery stenosis that might account for progressive azotemia. While specific forms of fibrous and/or atherosclerotic renal artery disease can lead to a compromise in renal function, differences may exist in the age of presentation, predominat sex, angiographic appearance and overal natural history. Recognition of these differences is helpful in deciding on the most likely lesion type, appropriate workup and treatment. Since renal artery stenosis can lead to radiologic and functional alterations, clinical markers of progression, such as renal size and serum creatinine measurements, are helpful in identifying patients with advancing disease. The regulators of fibrous disease progression are less clear than those responsible for atherosclerotic progression in the renal artery. Uncontrolled systemic hypertension, intrarenal hypertension, hyperlipidemia, cigarette smoking, and obesity all may potentially contribute to progressive atherosclerosis. Individuals identified with progressive azotemia due to renal artery stenosis may benefit from improved perfusion flow by renal revascularization or balloon angioplasty provided no significant parenchymal disease is present.     

Renovascular hypertension

Renovascular hypertension is the most common cause of secondary hypertension. Interest in identifying patients with renal artery stenosis has been stimulated recently by advances in three areas. First, is the realization that not only can renal artery stenosis cause renovascular hypertension, but it can also lead to progressive renal failure (ischemic nephropathy) caused by progression of disease, usually atherosclerotic in nature. Second, advances in percutaneous transluminal renal angioplasty and, especially, the recent use of renal stents has led to a less invasive management of these patients as compared with traditional renal revascularization. Finally, the development of newer less invasive diagnostic techniques, both for the identification of patients with renal artery stenosis and to follow patients with known renal artery stenosis, has simplified the diagnostic aspect of the disease.     

Pathogenesis and management of renovascular hypertension and ischemic nephropathy

Renovascular disease is an important cause of secondary hypertension and renal impairment. Atherosclerotic renal artery stenosis (ARAS) is the most important cause of renal artery stenosis (RAS), and has been linked to increased cardiovascular risk. The pathogenesis of renovascular hypertension is complex, but is mainly due to the over-activation of Renin-Angiotensin-Aldosterone system. A major consequence of untreated RAS is ischemic nephropathy, which is due to the sustained reduction in renal perfusion leading to derangement of microvascular function, and eventual development of interstitial fibrosis. Diagnosis of these conditions can be complex, sometimes needing invasive testing. Aggressive medical management is key to preventing progression of disease, as the role of revascularization in the management of ARAS is still not well defined.     

Atherosclerotic renovascular disease: diagnosis and treatment

The technical expertise and tools required to treat renovascular obstruction have become commonplace, and many series of patients revascularized with surgery, balloon angioplasty or endovascular stenting have been reported. Nevertheless, although hypertension and renal failure are easy to diagnose, their cause often remains elusive. Evidence is developing that patients with hypertension and atherosclerotic renal artery stenosis may often have hypertension and renovascular disease but not hypertension because of renovascular disease. As a result, diagnosis and therapy are increasingly directed towards the preservation of renal function, and the future of renal revascularization will depend on how well potential therapies address this goal.     

Atherosclerotic renal artery stenosis: epidemiology,cardiovascular outcomes,and clinical prediction rules

Atherosclerotic renal artery stenosis is the most common primary disease of the renal arteries, and it is associated with two major clinical syndromes, ischemic renal disease and hypertension. The prevalence of this disease in the population is undefined because there is no simple and reliable test that can be applied on a large scale. Renal artery involvement in patients with coronary heart disease and/or heart failure is frequent, and it may influence cardiovascular outcomes and survival in these patients. Suspecting renal arterial stenosis in patients with recurrent episodes of pulmonary edema is justified by observations showing that about one third of elderly patients with heart failure display atherosclerotic renal disease. Whether interventions aimed at restoring arterial patency may reduce the high mortality in patients with heart failure is still unclear because, to date, no prospective study has been carried out in these patients. Increased awareness of the need for cost containment has renewed the interest in clinical cues for suspecting renovascular hypertension. In this regard, the DRASTIC study constitutes an important attempt at validating clinical prediction rules. In this study, a clinical rule was derived that predicted renal artery stenosis as efficiently as renal scintigraphy (sensitivity: clinical rule, 65% versus scintigraphy, 72%; specificity: 87% versus 92%). When tested in a systematic and quantitative manner, clinical findings can perform as accurately as more complex tests in the detection of renal artery stenosis.     

Epidemiology and clinical presentation

Renovascular disease appears to be increasing in prevalence, particularly in older subjects with atherosclerotic disease elsewhere. Its clinical manifestations and presentation are changing because of rapid advances in medical therapy and other comorbid events. Although fibromuscular dysplasia and other diseases affecting the renal artery can produce the syndrome of renovascular hypertension, atherosclerotic renal artery stenosis is the most common clinical entity. It can produce a spectrum of manifestations, ranging from asymptomatic ("incidental"), identified during angiographic evaluation of other conditions, to progressive hypertension to accelerated cardiovascular disease with pulmonary edema and advanced renal failure. With the widespread application of drugs which block the renin-angiotensin system, including angiotensin-converting enzyme inhibitors and angiotensin antagonists, many cases of renovascular hypertension remain unsuspected and never produce adverse effects. Clinicians need to be alert to the potential for disease progression, with the potential for total renal artery occlusion and/or loss of viable renal tissue. Selection of patients for renal revascularization depends on individual balance of risks and benefits regarding the likely outcomes regarding both improvements in blood pressure control and preservation of renal function.     

Revascularization for atherosclerotic renal artery stenosis: the treatment of choice?

Atherosclerotic renal artery stenosis (ARAS) is an important cause of renal dysfunction and secondary hypertension, and is associated with adverse cardiovascular events and increased mortality. The natural history of ARAS is characterized by anatomic disease progression and/or renal dysfunction in only a minority of patients. Medical therapy for ARAS is directed primarily toward blood pressure control and cardiovascular risk factor reduction. Renal artery revascularization is an additional treatment option for ARAS associated with ischemic nephropathy or severe, poorly controlled hypertension despite aggressive medical therapy. Unfortunately, the benefits associated with revascularization versus medical therapy alone remain unproven. Renal artery revascularization may be accomplished through open surgical revascularization or angioplasty and stenting. Although surgical renal revascularization is associated with more durable results and relatively lower risk for postoperative renal function decline, the increased risk of death or major complications associated with this management approach limit its use in patients with significant comorbidities. Renal artery angioplasty and stenting is being utilized with increasing frequency but is of uncertain benefit and is associated with rates of post-intervention renal function improvement and deterioration that are approximately equal. Renal function outcomes associated with angioplasty and stenting may be improved through a selective treatment approach and utilization of distal embolic protection. Renal artery revascularization represents the only treatment alternative for patients unresponsive to medical management, and is therefore the 'treatment of choice' in this select group. Results of ongoing randomized trials are eagerly anticipated and may provide useful guidance for future management of ARAS.     

Renal artery stenosis and chronic ischemic nephropathy: epidemiology and diagnosis

Atherosclerotic renal artery stenosis (RAS) is the most common primary disease of the renal arteries and results in renovascular hypertension and ischemic nephropathy. Ischemic nephropathy from atherosclerotic RAS is increasingly recognized as a cause of chronic kidney disease (CKD) and in severe cases can lead to end-stage renal disease. The exact prevalence of atherosclerotic RAS is unknown because the disease is often asymptomatic and few are screened unless they have significant traditional cardiac risk factors or symptoms. A high prevalence of atherosclerotic RAS is seen in patients with advanced age, congestive heart failure, and extrarenal atherosclerosis. The primary reason for diagnosing ischemic nephropathy from renovascular disease is that the loss of kidney function is potentially reversible through treatment of the occlusion with surgical revascularization or percutaneous transluminal renal angioplasty. However, the benefits of revascularization have to be considered in the context of other comorbid disease and remain controversial. There are several tests available for the screening and diagnosis of atherosclerotic RAS; however, the diagnostic test of choice should be based on patient factors and institutional expertise because the best test is the one performed most often at the individual medical facility.     

Iatrogenic disease in elderly. Case report

Longer life expectancy and modern diagnostic and therapeutic advances favoured the ever more frequent development of ischaemic nephropathy (IN) characterized by the presence of atherosclerotic stenosis in both renal arteries (ARAS); 7% of patients older than 65 years with cardiovascular risk factors have ARAS but the prevalence grows to 20% in patients with coronary artery disease, to 42% in patients with aorto-iliac disease and to 67.5% in patients with peripheral artery atherosclerotic disease. Moreover the patient is later diagnosed with IN until de-hydratation or treatment with angiotensin converting enzyme inhibitors or angiotensin-2-receptor inhibitors. This therapy may present a hazard for elderly patients with unsuspected atherosclerotic renovascular disease; the risk may grow if nonsteroidal anti-inflammatory drugs are associated. Long life expectancy, associated comorbidities, multi-medication and functional failures induce a high risk for iatrogenic disease in elderly.     

The benefit of STent placement and blood pressure and lipid-lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery. The STAR-study: rationale and study design

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is associated with progressive loss of renal function and is one of the most important causes of renal failure in the elderly. Current treatment includes restoration of the renal arterial lumen by endovascular stent placement. However, this treatment only affects damage caused by ARAS due to the stenosis and ensuing post-stenotic ischemia. ARAS patients have severe general vascular disease. Atherosclerosis and hypertension can also damage the kidney parenchyma causing renal failure. Medical treatment focuses on the latter. Lipid-lowering drugs (statins) could reduce renal failure progression and could reduce the overall high cardiovascular risk. The additional effect on preserving renal function of stent placement as compared to medical therapy alone is unknown. Therefore, the STAR-study aims to compare the effects of renal artery stent placement together with medication vs. medication alone on renal function in ARAS patients. METHOD: Patients with an ARAS of > or = 50% and renal failure (creatinine (Cr) clearance < 80 mL/min/1.73 m2) are randomly assigned to stent placement with medication or to medication alone. Medication consists of statins, anti-hypertensive drugs and antiplatelet therapy. Patients are followed for 2 yrs with extended follow-up to 5 yrs. The primary outcome of this study is a reduction in Cr clearance > 20% compared to baseline. This trial will include 140 patients.     

Changing concepts in the surgical management of renovascular hypertension

Summary As newer surgical techniques and concepts have emerged, including revascularization of the totally occluded renal artery and alternatives to aortorenal bypass (hepatic, splenic, or iliac artery to renal artery grafts), our patient population has changed dramatically. Patients with diffuse atherosclerotic disease, bilateral renal artery stenosis, totally occluded renal arteries, and azotemia are more commonly referred for renal revascularization, thereby changing the indications for operation and the results that can be anticipated. Although our results in patients undergoing surgery solely for uncontrollable hypertension or renal failure have been successful, much work needs to be done to improve the results obtained in patients with a combination of uncontrollable hypertension and renal failure.     

Long-term outcome after surgical kidney revascularization for fibromuscular dysplasia and atherosclerotic renal artery stenosis

PURPOSE: At a time of minimally invasive surgery in urology, the role of surgical kidney revascularization in the management of renal artery disease has changed during the last decade. Our experience with surgical kidney revascularization, and the long-term clinical outcomes of fibromuscular dysplasia (FMD) and atherosclerotic renal artery stenosis are reviewed. MATERIALS AND METHODS: The study group comprised 140 patients with renovascular hypertension, 72 with FMD and 68 with atherosclerotic renal artery disease, who underwent surgical revascularization between 1982 and 1999. The indications for surgical revascularization were the treatment of hypertension and the preservation of renal function in 17 patients with renal artery occlusion, 55 with ostial stenosis, 52 with branch stenosis, 6 with bilateral artery stenosis, 7 with solitary kidney renal artery stenosis and 3 with solitary kidney renal artery occlusion. RESULTS: Postoperative blood pressure and renal function were monitored for 1 to 17 years (mean 11.3). Long-term blood pressure control was observed in 93% of patients with FMD and in 71% of those with atherosclerosis. Improvement or stabilization of renal function was observed in 92% of patients with FMD and in 68% of those with atherosclerosis. The preoperative estimated glomerular filtration rate compared to postoperative was significantly increased in both groups. CONCLUSIONS: Surgical kidney revascularization is effective in secondary hypertension with a high long-term efficacy in the normalization of blood pressure and in the preservation of renal function, especially in patients with a solitary or 1 functional kidney.     

Is incidental renal arteriography justified in a population of patients with symptomatic peripheral arterial disease?

Renal artery stenosis is a consequence of generalized atherosclerosis and many specialists perform routine selective renal angiography to detect and treat renal artery stenosis. The incidence of clinically important renal artery stenosis is not well defined in patients with symptomatic peripheral arterial disease. The purpose of this study was to better delineate the incidence of and the risk factors associated with renal artery stenosis, renovascular hypertension, and ischemic nephropathy incidentally discovered during angiography for symptomatic peripheral arterial disease. Two hundred consecutive patients undergoing angiographic evaluation of symptomatic lower extremity peripheral arterial disease were studied retrospectively. Angiograms were reviewed for the presence of renal artery stenosis (defined as >or= 25% diameter reduction in either renal artery) and findings were then correlated to the clinical diagnosis of renovascular hypertension (> 50% renal artery stenosis and >or= 3-drug resistive hypertension) and ischemic nephropathy (defined as > 50% bilateral renal artery stenosis, 3-drug hypertension, and creatinine >or= 1.5). Angiographic findings were also correlated with risk factors to determine if a relationship correlated to the presence of and degree of renal artery stenosis. Data were analyzed using the Student's t test, Chi-square model, and multiple logistic regression analysis. The overall incidence of any degree of renal artery stenosis in this study population was 26% (52 patients). Only 24 (12%) patients had an incidental finding of >or= 50% stenosis in either renal artery. Six (3%) of these patients were found to have associated renovascular hypertension. Additionally, 9 (4.5%) patients had coexistent renal insufficiency and significant renal artery stenosis; five with end-stage renal disease on chronic hemodialysis. Only one patient with end-stage renal disease had poorly controlled 3-drug hypertension. Thus definitive ischemic nephropathy was present in only one (0.5%) patient. Statistically significant risk factors associated with the presence of renal artery stenosis include hypertension (P < .001), coronary disease (P = .024), female gender (P = .010), diabetes (P = .039), aorto-iliac disease (P = .031), multiple levels of peripheral arterial disease (P < .001), and age over 60 ( P < .001). While the incidence of renal artery stenosis in patients being evaluated for symptomatic peripheral arterial disease is similar to that reported in the cardiology literature, the incidence of renovascular hypertension and ischemic nephropathy is exceedingly low (3% and 0.5%, respectively)-findings similar to data reported in the general hypertensive population. These data suggest that incidental selective renal angiography is not justified in patients with symptomatic peripheral arterial disease.     

Atheroembolic renal disease: effect on morbidity and survival after revascularization for atherosclerotic renal artery stenosis

PURPOSE: Atheroembolic renal disease is increasingly found in older patients with general atherosclerosis. We evaluated the impact of atheroembolic renal disease on morbidity and survival after surgical revascularization for atherosclerotic renal artery stenosis. MATERIALS AND METHODS: The study group comprised 44 patients who underwent surgical revascularization for atherosclerotic renal artery stenosis and concomitant intraoperative renal biopsy. Renal biopsy specimens were reviewed by a pathologist and evaluated for the presence or absence of atheroemboli, and the presence and severity of arteriolar nephrosclerosis. Postoperative patient data were reviewed to evaluate survival, and the incidence of renal and systemic morbid events. Patients were followed for 1 to 14.5 years (median 6.2) after surgical revascularization. RESULTS: Atheroembolic renal disease was identified in the intraoperative biopsy specimen in 16 patients (36%, group 1) and was absent in 28 (64%, group 2), termed groups 1 and 2. Atheroembolic renal disease correlated significantly with decreased patient survival. The 5-year survival in groups 1 and 2 was 54 and 85%, respectively (p = 0.011). Similarly the incidence of systemic atherosclerotic complications was significantly higher in group 1 than group 2 (86 versus 58%, p <0.05). In addition, renal or renovascular complications developed in more group 1 than group 2 patients (p = 0.07). There was no significant association between the presence or severity of arteriolar nephrosclerosis and postoperative survival or morbid events. CONCLUSIONS: Our results indicate that atheroembolic renal disease is associated with decreased survival and an increased incidence of atherosclerotic morbid events after surgical revascularization for atherosclerotic renal artery stenosis. This information may be useful for therapeutic decision making in patients with atherosclerotic renal artery stenosis.     

Management of High Blood Pressure in Peripheral Arterial Disease

Arterial hypertension (HTA) is a promoter of peripheral arterial disease (PAD) in association with other atherosclerotic risk factors. Systolic HTA is the most frequently noted form in such disease, secondary to marked increase in large artery stiffness.

The existence of PAD confers on the hypertensive patient a very high cardiovascular (CV) risk, requiring an intensive global therapeutical approach. Treating HtA is one of such beneficial actions. The optimal blood pressure (BP) to be reached is at least < 140/90 mmHg but lower BP should be targeted if possible (< 130/80 mmHg). First of all, a modification of the lifestyle and diet should be proposed. But to reach such a low target, different antihypertensive agents must be very often used in association. The inhibitors of the renin-angiotensin system constitute one of the main axis of such drug treatment, after having avoided the pitfall of renal artery stenosis.     

Management of high blood pressure in peripheral arterial disease

Arterial hypertension (HTA) is a promoter of peripheral arterial disease (PAD) in association with other atherosclerotic risk factors. Systolic HTA is the most frequently noted form in such disease, secondary to marked increase in large artery stiffness. The existence of PAD confers on the hypertensive patient a very high cardiovascular (CV) risk, requiring an intensive global therapeutical approach. Treating HTA is one of such beneficial actions. The optimal blood pressure (BP) to be reached is at least < 140/90 mmHg but lower BP should be targeted if possible (< or = 130/80 mmHg). First of all, a modification of the lifestyle and diet should be proposed. But to reach such a low target, different antihypertensive agents must be very often used in association. The inhibitors of the renin-angiotensin system constitute one of the main axis of such drug treatment, after having avoided the pitfall of renal artery stenosis.