Hypertension and atherosclerotic renal artery stenosis: diagnostic approach

Atherosclerotic renovascular disease needs noninvasive diagnostic tools to apply to patients having clinical characteristics that can suggest its presence. Color Doppler ultrasonography is a noninvasive, inexpensive diagnostic procedure that is capable, in an experienced hand, of accurately screening for renovascular disease. Magnetic resonance angiography and spiral computed tomography angiography play an ancillary role in detecting atheromatous renovascular disease. Captopril-enhanced renography and scintigraphy and the resistive index at Doppler sonography may be very useful in patients with renal artery stenosis for predicting the response to revascularization.     

Renovascular disease and renal insufficiency--diagnosis and treatment

Renovascular disease as cause of end-stage renal disease has become more frequent during the last decade. In order to minimize the need for dialysis treatment non-invasive screening for the disease is needed. However, both ultrasonic duplex scanning and renal scintigraphy are not sufficient for detection of all stenosis. Furthermore, there is little data on non-invasive tests in patients with renal insufficiency. Renal arteriography is the gold standard for detection of renovascular disease. One disadvantage is the risk of contrast-agent induced acute renal insufficiency. This problem can be avoided using carbon dioxide angiography. In the near future spiral computed tomography and magnetic resonance angiography may be alternatives for identifying patients with renovascular disease. Ischaemic nephropathy is potentially curable. Percutaneous transluminal renal angioplasty is first line treatment in most cases. Intervention often results in improvement or preservation of renal function which is very important in order to avoid chronic dialysis.     

Diagnostic criteria for renovascular disease: where are we now?

Renovascular disease, especially atherosclerotic renal artery stenosis (ARAS) in older subjects, is commonly encountered in clinical practice. This is at least in part due to the major advances in non-invasive imaging techniques that allow greater diagnostic sensitivity and accuracy than ever before. Despite increased awareness of ARAS, renal revascularization is less commonly performed, likely as a result of several prospective, randomized, clinical trials which fail to demonstrate major benefits of renal revascularization beyond medical therapy alone. Primary care physicians are less likely to investigate renovascular disease and nephrologists likely see more patients after a period of unsuccessful medical therapy with more advanced ARAS. The goal of this review is to revisit current diagnostic and therapeutic paradigms in order to characterize more clearly which patients will likely benefit from further evaluation and intensive treatment of renal artery stenosis.     

Captopril-enhanced renal scintigraphy in the diagnosis of pediatric hypertension

Hypertension in childhood is no longer a rare condition mainly secondary to renal, or renovascular diseases, as a growing proportion of children are obese and hypertensive, with the phenotype of metabolic syndrome. Thus, we need to reconsider our practice in the examination of the hypertensive child and redefine the place of non-invasive methods for screening of renovascular hypertension, and specifically, to evaluate the value of captopril-enhanced renal scintigraphy at the two ends of the palette: the obese child with hypertension and the severely hypertensive prepubertal child. Renal artery stenosis in children is mainly due to fibromuscular dysplasia and stenoses associated with syndromes involving single or multiple smaller branch vessels. This explains the low specificity and sensitivity of the color-Doppler ultrasound method and captopril renal scintigraphy. Even the more sophisticated computed tomography (CT) and magnetic resonance imaging (MRI) angiographic techniques are, at present, not sensitive enough to exclude stenoses of the small branches definitely. Thus, children in whom there is a strong suggestion of renovascular hypertension should undergo angiography with a view to endovascular treatment, as non-invasive imaging has no significant benefit and might lead to a delay in treatment. In the cases when the probability of renovascular disease is moderate a basic assessment of renal function and structure is sufficient. In the neonate, catheter-associated thromboembolic disease is among the most common causes hypertension. It should be controlled medically until the patient is old enough to undergo angiography and angioplasty successfully. Thus, in this age group, there is a place for functional imaging with renal sonography and angiotensin-converting enzyme inhibitor (ACEI) renography to detect hemodynamically significant renovascular disease, with the limitations mentioned above. However, the rapid technical evolution of non-invasive methods requires periodic re-consideration of the actual standpoints.     

Digital subtraction angiography for noninvasive imaging of the renal artery

Digital subtraction angiography (DSA) is a relatively new radiologic technique for noninvasive imaging of arterial anatomy. DSA has been shown to be effective in defining the renal arteries in patients with known or suspected renovascular disease. DSA is an excellent means of screening for renovascular disease and of following patients with serial studies after surgical revascularization or percutaneous dilatation of renal arterial stenosis. It is excellent for monitoring patients with known renovascular disease.     

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.     

Captopril renal scintigraphy--an advance in the detection and treatment of renovascular hypertension

Despite the risks associated with renovascular hypertension and the durable benefits of revascularization, the detection of patients with renovascular hypertension and the selection of those who will benefit from interventional therapy remains a challenge. We have previously documented the reliability of captopril renal scintigraphy in predicting angiographically significant renal artery stenosis in patients suspected of having renovascular hypertension. In the present study we report our recent experience with this noninvasive technique in predicting outcome after revascularization. Captopril renal scintigraphy involves the administration of 50 mg of captopril 3 hours after a baseline technitium-99m diethylenetriaminepentaacetic acid renal scan and 1 hour before a repeat captopril renal scintigraphy scan. Nineteen of the last 70 patients with clinically suspected renovascular hypertension undergoing captopril renal scintigraphy had abnormal renal scan outcomes, and 17 had a decrease in flow or function after captopril (positive captopril renal scintigraphy). Eight of these 17 with abnormal findings on captopril renal scintigraphy underwent revascularization, and the hypertension was cured or improved in six of the eight: two of three after surgical bypass grafting and four of five after angioplasty. In the seven surviving patients with abnormal renal scan results but no change with captopril (negative captopril renal scintigraphy), improvement in hypertension after treatment occurred in only one: one of two after nephrectomy, zero of three after bypass surgery, and zero of two after angioplasty (p less than 0.05). We conclude that captopril renal scintigraphy is an accurate predictor of hypertension response to revascularization. Further evaluation of this new noninvasive technique for assessing patients with suspected renovascular hypertension appears warranted.     

Captopril-enhanced 99mTc DTPA Scintigraphy in the Detection of Renal-artery Stenosis

The value of captopril-enhanced ^99mTc DTPA scintigraphy as ascreening test for renovascular disease was prospectively studiedin 44 hypertensive patients suspected to have renal-artery stenosis.Renal impairment (plasma creatinine >130umol/l) was presentin 29 patients. At angiography 13 patients had unilateral stenosis,two bilateral stenosis, and 29 patients had no renovasculardisease. Captopril induced a fall in split renal function inthe kidney ipsilateral to the stenosis in all patients withunilateral disease (mean 52 ± 23% to 44 ± 21%of total renal function; P <0.001). A positive captoprilscintigram (defined as a fall of 5% or more in split renal function)had a sensitivity of 85% and a specificity of 72% in the detectionof unilateral renal-artery stenosis. Captopril-enhanced ^99mTcDTPA scintigraphy is a promising non-invasive screening testfor the detection of renal-artery stenosis.     

Renovascular hypertension: predicting surgical cure with exercise renography

Renal artery stenosis with resultant renovascular hypertension has attracted clinical attention because the disease is potentially curable and because numerous diagnostic and therapeutic modalities compete for clinical acceptance. An exercise-mediated disturbance of renal hippurate transport was recently described, and has been implicated as having a role in nephrogenic fixed hypertension. To predict the final course of renovascular hypertension before operation we carried out a prospective study with the goal of verifying the predictive value of exercise hippurate scintigraphy. The study was to test the hypothesis that patients with disturbance of renal hippurate transport (pathologic renogram) induced by exercise would have stabilized hypertension and would continue to be hypertensive after operation. Thirty-one patients with hypertension who had unilateral or bilateral renovascular stenosis documented on angiography were referred to rest and exercise hippurate scintigrams before operation. The results of the examinations at rest served as standard and were compared with the exercise scintigrams. In 19 of the 31 (61%) patients a disturbance of transrenal hippurate transport evolved during exercise, whereas 12 (39%) patients failed to respond to exercise with altered hippurate kinetics. Twenty-six patients went on to renovascular operations; five had percutaneous transluminal angioplasty. Revascularization results differed markedly when the blood pressure response of patients with positive results on exercise (abnormal) and patients with negative results on exercise (normal) were compared. Ten of 12 patients with hypertension who had normal exercise renograms were cured. In comparison, blood pressure values were little influenced by therapy in patients with an abnormal response, where 17 of 19 patients continued to have hypertensive disease after therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic procedure in renovascular hypertension

Detection of a renal artery stenosis (RAS) as a cause of arterial hypertension is of great practical importance because dilatation of the stenosis frequently results in an improvement or cure of the hypertension. In recent years, a number of screening procedures aimed at diagnosing renovascular hypertension have been developed, e.g., duplex sonography of the renal arteries, determination of plasma renin activity, or renal scintigraphy following administration of captopril. The possibilities and limitations of these screening procedures are described here. The best method for detecting renal artery stenosis is angiography, which can now be performed on an outpatient basis, using thin catheters.     

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.     

Pre- and postcaptopril renal scintigraphy as a screening test for renovascular hypertension in children

We studied the ability of pre- and postcaptopril renal scintigraphy to predict renovascular disease (RVD) in children. Retrospective review of medical notes and radiology reports of all hypertensive children who had had both pre- and postcaptopril renal scintigraphy with [^99mTc] dimercaptosuccinic acid (DMSA) and/or [^99mTc] mercaptoacetyltriglycine (MAG3) and digital subtraction angiography (DSA). 81 children aged 1–18 (median 10) years were studied with 62% (51) having a diagnosis of RVD. Main renal artery disease, intrarenal disease, and both main and intrarenal artery disease were present in 25, 14, and 12 patients respectively. The isotope study accurately diagnosed RVD, confirmed by DSA, in 47% (24 of 51) children, with eight false positive studies. The sensitivity, specificity, and positive and negative predictive values of the isotope study to predict RVD were 48%, 73%, 76%, and 51%, respectively. Pre- and postcaptopril renal scintigraphy was unable to predict RVD in children.     

Acute renal thrombosis induced by angiotensin-converting enzyme inhibitors in patients with renovascular hypertension

Acute reversible renal failure is a widely recognized potential complication of angiotensin-converting enzyme inhibitor (ACEI) administration in renovascular hypertension, particularly in bilateral artery stenosis or stenosis involving a solitary kidney. We report herein 2 cases of a rare but severe complication, i.e., acute renal artery thrombosis. Whereas marked hypotension does not seem to be necessary to trigger acute renal failure following ACE inhibition, by contrast, the fall in blood pressure could play an important role in our patients. Since single-dose ACEI has been advocated in order to improve the predictive value of renal scintigraphy or plasma renin activity measurements in the diagnosis of renovascular hypertension, the potential risk of this approach should be stressed.     

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.     

Novel noninvasive techniques for studying renal function in man

Renal artery stenosis is a major cause of renovascular hypertension in humans, and may lead to ischemic nephropathy and end-stage renal disease. The mechanisms responsible for the progressive renal functional and structural alterations have not been fully elucidated, partly because of the lack of reliable, noninvasive techniques capable of quantifying renal regional hemodynamics and function distal to a stenosis in the renal artery. Novel imaging tools now enable quantification of concurrent intrarenal (cortical and medullary) hemodynamics, segmental nephron dynamics (intratubular transit times and fluid concentrations), and renal function in the intact kidney. Fast computed tomography (CT) scanners, such as electron beam CT, allow discrimination of subtle alterations in renal perfusion and segmental nephron function consequent to changes in renal perfusion pressure, both within and below the range of renal blood flow autoregulation. This technique provides an opportunity to define intrarenal perfusion patterns and function in animals and patients with renal artery stenosis, and may provide insight into the effects of chronic unilateral or bilateral renovascular disease on both the hypoperfused and contralateral kidneys. This methodology may thereby prove to be very useful in the evaluation of renal disease in general, and the renovascular hypertensive patient in particular.     

Renovascular hypertension following renal transplantation

The authors address the multifactored origins of renovascular hypertension following renal transplantation and present the experience with digital subtraction angiography and percutaneous transluminal angioplasty as well as standard angiography and surgical repair in the diagnosis and treatment of transplant renal artery stenosis. The roles of the renin-angiotensin system of the native kidney and of the allograft in sustaining hypertension after transplantation are reviewed in detail.     

Ischemic nephropathy: detection and therapeutic intervention

Although the real prevalence of ischemic nephropathy as a cause of end-stage renal disease is unknown, its incidence has increased in past years. The diagnosis of this pathology requires that a number of functional and anatomic tests be carried out. The initial approach should be to perform duplex Doppler ultrasonography which, besides providing data on the size and extent of the stenosis, enables the intrarenal resistive index to be estimated to determine the pattern of renal parenchyma injury and the expected progression if revascularized. The most frequently used morphologic techniques are magnetic resonance angiography and computer tomography angiography. In the event of ischemic neuropathy, it is necessary to perform a renal arteriography regardless of the inherent risks of contrast toxicity or atheroembolism. Various therapeutic options are reviewed, with emphasis on percutaneous transluminal renal angiography plus stent as the first indication. Even though initial reports were contradictory, several meta-analyses have concluded that better blood pressure control and renal function improvement are achieved with percutaneous transluminal renal angiography plus stent than with conventional medical therapy. Surgical revascularization is preferable in patients with severe aorto-iliac pathology and renal artery ostium complete thrombosis. The risks and benefits of these procedures must be evaluated on an individual basis.     

New diagnostic techniques for imaging the renal arteries

There has been an increasing focus on renovascular disease, particularly in renal failure, and on the role of renal angioplasty and stenting. Significant improvements have occurred in non-invasive imaging techniques. This review concentrates on the recent developments in imaging that specifically targets the renal artery and renal artery stenosis. It also discusses how these techniques may facilitate better selection of cases that will respond to intervention.     

Ischemic nephropathy: where are we now?

Identification and reversing the loss of kidney function beyond occlusive disease of the renal arteries poses a major clinical challenge. Recent studies indicate that atherosclerotic renal artery stenosis develops as a function of age and is commonly associated with other microvascular disease, including nephrosclerosis and diabetic nephropathy. The risks of renal artery stenosis are related both to declining kidney function and to accelerated cardiovascular disease, with increased morbidity and mortality. Newer drugs, including agents that block the renin-angiotensin system, have improved the level of BP control for renovascular hypertension. Progressive renovascular disease during medical therapy can produce refractory hypertension, congestive heart failure, and renal failure with tubulointerstitial fibrosis. Recent studies indicate a complex interplay of oxidative stress, endothelial dysfunction, and activation of fibrogenic cytokines as a result of experimental atherosclerosis and renal hypoperfusion. Advances in imaging and interventional devices offer major new opportunities to prevent progressive loss of kidney function. Recent series indicate that although 25 to 30% of patients with impaired renal function can recover glomerular filtration after revascularization, many have no apparent change in kidney function and 19 to 25% experience a significant loss of kidney function, in some cases as a result of atheroemboli. To select patients who are most likely to benefit from vascular intervention, clinicians should understand the pathophysiology of developing ischemic nephropathy and the potential hazards of revascularization in the setting of diffuse atherosclerotic disease. Further research should be directed toward identification of critical disease, regulation of fibrogenesis, and the interaction with other atherosclerotic processes.     

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.