Renovascular hypertension (RVHT) denotes nonessential hypertension in which a causal relationship exists between anatomically evident arterial occlusive disease and elevated blood pressure (see the images below). RVHT is the clinical consequence of renin-angiotensin-aldosterone activation as a result of renal ischemia. Renal artery stenosis (RAS) is a major cause of RVHT and accounts for 1-10% of the 50 million cases of hypertension in the United States.
Apart from the casual relationship of occlusive renal artery disease and hypertension, RAS is also being increasingly recognized as an important cause of chronic renal failure. In older patients, atherosclerosis is the most common cause of RAS. RAS caused by atherosclerosis is generally a progressive disease with increasing luminal narrowing, which may eventually compromise renal blood flow and renal function and structure.
Arterial dysplasias (AD) are an uncommon angiopathy associated with heterogeneous histologic changes that may affect the carotid circulation and the visceral and peripheral arteries. Medial fibroplasia (MFP), as a cause of RAS, usually affects young to middle-aged adults, mostly women, but it can also affect children. It is an important cause of RVHT in children. [1, 2, 3, 4] The average age range of patients with MFP is 30-40 years. The youngest patient with MFP of the renal artery was reportedly 6 months of age.
Ultimately, MFP results in arterial stenosis, which causes organ ischemia or infarction. The clinical manifestations reflect the arteries involved; it most commonly manifests as hypertension caused by RAS or as strokes caused by carotid artery disease. MFP is one of the most important mimics of vasculitis.
Although MFP is a pathologic diagnosis, characteristic change is seen at vascular imaging. The most common finding is the string-of-beads appearance, caused by areas of relative stenoses or webs alternating with small fusiform or saccular aneurysms of the artery. Approximately 10-30% of patients with RAS have MFP.
Diagnostic imaging plays an essential role in the diagnosis and treatment of RVHT. With an aging population and a possible increase in the prevalence of RAS and ischemic nephropathy, radiologists will play an increasing role in both the diagnosis and treatment of RVHT. [5, 6, 7, 8]
The preferred imaging method for a patient suspected of having RAS is controversial. Accurate identification of patients with correctable RVHT can be difficult with use of standard noninvasive techniques, such as sonography, because they provide only indirect evidence of the presence of RAS. On the other hand, some invasive techniques that are much more accurate have the potential of nephrotoxicity. In such cases, invasive methods can cause deterioration of renal function and procedure-related complications at the site of arterial puncture or catheter-induced embolism.
Gilfeather et al evaluated conventional angiography versus gadolinium-enhanced magnetic resonance angiography (MRA) in 54 patients and 107 kidneys. The study showed that in 70 kidneys (65%), the average degree of stenosis reported for both modalities differed by 10% or less. 
In 22 cases (21%), MRA caused overestimation of the stenosis by more than 10% relative to the results of conventional angiography. In 15 cases (14%), MRA caused underestimation of the stenosis by more than 10%. MRA produces excellent contrast-enhanced angiograms without the risk of iodinated compounds and radiation exposure. MRA provides accurate information about the number of renal arteries, the size of the kidneys, and the presence of anatomic variants. The obvious advantages of conventional angiography are its usefulness in determining the clinical importance of suspicious lesions and the ability to concurrently perform endovascular intervention.
Hypertensive urography is of historical interest and is no longer used as a screening technique for RAS. CO2 angiography is also obsolete, because of MRA and gadolinium imaging. Computed tomography angiography (CTA) with maximum intensity projection (MIP) and the quantitative measurement of stenosis is an accurate, noninvasive technique in the diagnosis of visceral artery stenosis; this is fast becoming the diagnostic tool of choice, with angiography being reserved for cases in which vascular intervention is planned. [10, 11]
Doppler ultrasonography can be used to measure the velocity of blood flow. It is a noninvasive technique, and it has high sensitivity in expert hands. Color-flow Doppler may demonstrate disorganized flow patterns and high-velocity flow stream associated with hemodynamically significant stenosis.  Radionuclide renography technetium (Tc)-mercaptoacetyltriglycine (MAG3)-captopril has a high sensitivity and specificity, and it adds a physiologic element to the diagnosis of RAS. 
The diagnosis of RAS is a frequent consideration when dealing with severe hypertension and renal failure; however, the benefits of screening and the choice of imaging modalities is controversial. US, CTA, and MRA are all used, and each method has its own advantages and drawbacks. Moreover, interpretation requires significant expertise. No consensus has been reached on the choice the imaging modality, and the decision should be based on the level of expertise available. 
Herrmann and Textor have recently reviewed the current state of renovascular disease, especially in older subjects in whom atherosclerotic renal artery stenosis is commonly encountered in part due to the major advances in noninvasive imaging techniques that allow greater diagnostic sensitivity and accuracy than ever before. Despite better diagnostic accuracy, renal revascularization is seldom performed, partly because of prospective, randomized, clinical trials that fail to demonstrate major benefits for renal revascularization beyond medical therapy alone. This review revisits current diagnostic and therapeutic scenarios in order to characterize more clearly which patients benefit from further evaluation and active intervention of RAS. 
Limitations of techniques
The acceptance of radionuclide renography as a primary screening tool for RAS has been hindered by the lack of standardized protocols. 
Doppler ultrasonography is operator dependent, time consuming, and cumbersome. Doppler sonography examination is affected by anatomic, technical, patient-related, and pathologic factors.
CTA or MRA may cause the clinician to overlook mild cases of fibromuscular dysplasia (FMD) that are detectable with digital subtraction angiography (DSA). Most of the false-negative and false-positive findings of RAS arise from accessory renal arteries. MRI is expensive, and its availability is limited.
Measurements of the size of RAS on angiograms (an important clinical consideration) are imprecise, and angiograms do not permit assessment of the cross-sectional area or, more importantly, the flow through the stenotic segment. The various histologic types of FMD are difficult to distinguish on angiograms; this limitation has important clinical implications from a prognostic point of view.
All techniques do not relate to the predictive value of the cure aspect in reestablishing renal perfusion.
For the detection of RAS, hypertensive urography is obsolete. Hypertensive urography is of historical interest only. It is no longer used as a screening technique for RAS because of its inconsistent results. The urogram may be normal in the presence of established RAS.
CTA with MIP and quantitative measurement of stenosis is an accurate noninvasive technique in the diagnosis of RAS. The advent of spiral and multisection computed tomography (CT) scanning has made CTA feasible. Continuous scanning through an area of interest during a single breath-hold provides sufficient data to reconstruct 3-dimensional (3D) images. For CT scans of a patient with Leriche syndrome, see the images below.
Many scanning protocols are available. The general consensus is that a timed bolus and a rapid injection rate improve image quality. No positive oral contrast material should be used because it results in severe degradation of the image quality. Immediately before the procedure, the patient ingests water, and glucagon is then given intravenously to diminish bowel movement and maximize bowel distention. The 3 most common techniques used for 3D reconstruction are MIP, shaded-surface display (SSD), and volume rendering. MIP is often the single most useful technique for 3D reconstructions.
The sensitivity and specificity of spiral CT in detecting RAS are approximately 98% and 94%, respectively. In patients with a plasma creatinine concentration higher than 1.7 mg/dL, the accuracy is lower (93% sensitivity, 81% specificity), possibly because of reduced renal blood flow. Because most of the false-negative and false-positive findings arise from accessory renal arteries, the accuracy in detecting RAS of the main renal artery may be as good as that of angiography.
Andreoni et al raised concerns that CTA or MRA may cause clinicians to overlook mild cases of DSA-detectable AD.  Most of the false-negative and false-positive findings of RAS are related to accessory renal arteries.
Magnetic Resonance Imaging
MRA is fast becoming a clinical standard for the safe and noninvasive detection of RAS, aneurysms, and occlusions.  A comprehensive examination includes 3D dynamic gadolinium-enhanced and 3D phase-contrast MRA techniques, which allow an evaluation of the renal arteries and other visceral arteries. The 3D phase-contrast technique is flow based and subject to dephasing in the presence of significant arterial stenosis. The 3D gadolinium-enhanced MRA method produces excellent contrast angiograms without the risk of iodinated compounds or radiation exposure. (See the images below.)
Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.
As of late December 2006, the FDA had received reports of 90 such cases of NSF/NFD. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.
Degree of confidence
Gadolinium-enhanced MRA has been proven to have high sensitivity for detecting stenosis in the main and accessory renal arteries. At presentation, MRA provides anatomic information regarding a vascular stenosis, but it provides little information about the functional significance of a stenosis. Studies have shown that 3D MRA with gadolinium-based contrast agents (which have a low potential for nephrotoxicity) has a sensitivity of 96-100% and a specificity of 71-96% for the detection of a main RAS of greater than 50%.
When combined with cardiac synchronization, 3D MRA can sharply delineate the entire length of the major renal arteries. However, MRA remains suboptimal for the detection of hemodynamically significant lesions of distal, intrarenal, and accessory renal arteries, which may cause physiologically significant RAS.
Limitations of MRA include its cost and lack of availability. Contraindications to MRA include claustrophobia and the presence of metallic implants, such as a pacemaker or surgical clip.
Andreoni et al raised concerns that CTA or MRA may cause clinicians to overlook mild cases of DSA-detectable AD.  Although false-negative studies in RAS are rare, a tendency to overestimate stenoses occurs, and this overestimation may lead to a false-positive diagnosis. To some extent, this tendency to overestimate stenoses can be compensated for by performing phase-contrast MRA, a type of MRA that utilizes accumulated phase differences.
The diagnosis of RAS is made on the basis of systolic and diastolic velocity changes throughout the length of the renal artery. The most reliable Doppler criteria for stenosis are a high-velocity jet and distal turbulence. (See the images below.) 
Renal artery flow patterns can be classified into 4 categories: (1) normal, (2) diameter-reducing stenosis of less than 60%, (3) diameter-reducing stenosis of more than 60%, and (4) renal artery occlusion.
The peak systolic velocity in normal renal arteries averages 120 cm/s ±12, with an average peak systolic aortic velocity of 60 m/s ±15. Both velocities decrease with age.
The kidneys have a low-resistance vascular bed; thus, the Doppler spectral waveform from the normal kidney is that of a constant forward diastolic flow. In renal parenchymal disease, there is increased vascular resistance, which causes a decrease in the diastolic flow component and an increase in the pulsatility of the Doppler spectral waveform. Parenchymal diastolic flow velocities of less than 20% of the peak systolic velocities are consistent with renal parenchymal disease.
In RAS, the peak systolic velocity increases by more than 150 cm/s for angles less than 60° and by more than 180 cm/s for angles greater than 70°. Poststenotic spectral broadening may be present with or without flow reversal. Flow may be absent during diastole in a stenosis of more than 50%. A ratio of the peak systolic renal artery velocity to the aortic peak systolic velocity of 3.5 or more is said to be predictive of a stenosis of more than 60%.
Certain indirect Doppler ultrasonographic signs have been described for RAS. One such sign is the presence of tardus-pavus pulse, which is demonstrated by a gradual slope of Doppler waveform during systole (pulse time increase of greater than 0.07-0.12 s) and an attenuation of Doppler waveform amplitude (peak systolic velocity less than 20-30 cm/s). The acceleration index is determined by dividing the slope of the systolic upstroke (in kilohertz per second) by the carrier Doppler frequency. The acceleration time is the interval between the onset of systole and the initial peak. The acceleration index in RAS is greater than 3 m/s2. The resistive index in RAS is usually less than 0.56. The early systolic peak may be absent in RAS.
Color-flow Doppler imaging may demonstrate disorganized flow patterns and a high velocity flow stream associated with hemodynamically significant stenosis. A false-negative diagnosis may occur with an accessory renal artery, whereas a false-positive diagnosis may be made with coarctation of the aorta.
In about 10% of patients who undergo renal transplantation, RAS occurs in the transplanted kidney. This raises the question of whether RAS is the cause of post-transplant hypertension. The site of stenosis is not an anastomotic site in most patients; this suggests the possibility of focal rejection (with edema/fibrosis) as the cause of the hypertension. Duplex and color-Doppler sonography have greatly affected the diagnosis of RAS.
Degree of confidence
Doppler ultrasonography has several limitations in the diagnosis of RAS. These include patient-related factors, anatomic factors, technical factors, and pathologic factors.
Patient-related factors include bowel gas, obesity, respiratory renal movements, and poor patient compliance.
Anatomic factors include multiple renal arteries (16-28%), variation of renal veins (used as imaging landmarks), horseshoe kidneys, and crossed ectopia.
Technical factors include false-positive examination results associated with suboptimal angles, variation in operator experience, incomplete examination (because complete renal evaluation is cumbersome), the need to visualize the entire length of artery, transmitted cardiac and/or aortic pulsation (which may obscure renal waveforms), and different emphases on variable parameters.
Pathologic factors include false tracings (which may be recorded from large collateral vessels and a reconstituted main renal artery) and the presence of disorders that are associated with RAS and that affect different sites (eg, atheroma, fibromuscular hyperplasia, vasculitis, arteriovenous fistula, retroperitoneal fibrosis, neurofibromatosis).
Standard renography with iodine-131 (131 I)–labeled ortho-iodohippurate (OIH) is of historical interest and is no longer performed in the investigation of RAS.
The effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on RAS was first described by Majd et al in 1983.  They observed virtually no radionuclide uptake on diethylene triamine pentaacetic acid (DTPA) images in a patient with hypertension receiving captopril therapy. A repeat DTPA renogram performed in the same patient after cessation of captopril therapy revealed normal, bilateral DTPA uptake.
A number of mechanisms have been proposed to explain the effects Majd et al observed,  although none explain the entire observed phenomenon. Normally, a balance maintains glomerular filtration in vascular tone between the preglomerular and postglomerular arterioles. With significant RAS, this balance is disturbed, because the pressure in the preglomerular arteriole is decreased and the filtration pressure can be maintained only by the postglomerular arteriolar vasoconstriction mediated by the renin-angiotensin system.
The administration of an ACE inhibitor such as captopril prevents the conversion of angiotensin I to the active vasoconstrictors angiotensin II and angiotensin III. By inhibiting the compensatory increase in vascular tone at the postglomerular arteriole, ACE inhibitors decrease glomerular filtration in the setting of RAS. The administration of ACE inhibitors in conjunction with radionuclide renography provides a noninvasive method for the detection of functionally significant RAS. [28, 29]
Several radiopharmaceuticals with different clearance mechanisms are available, although all show a degree of clearance via glomerular filtration. In particular, DTPA is primarily cleared by means of glomerular filtration. The decreased clearance of DTPA induced by ACE inhibitors in RAS, as Majd et al observed, is readily shown on renograms as a decrease in function in the affected kidney and a deterioration in the renogram curve. 
In patients with RAS, effective renal plasma flow (ERPF) is shown to increase after the administration of an ACE inhibitor because of the efferent arteriolar vasodilatation, which increases blood flow through the renal parenchyma and decreases blood flow through the glomerulus.131 I-labeled OIH also closely estimates ERPF. Tc-MAG3 has also been used to qualitatively assess ERPF. (See the image below.)
Since the introduction of captopril renography, various modifications have been made. Some centers use only 1 agent, either DTPA or MAG3. A positive result on ACE inhibition radionuclide scanning indicates that RVHT is present; it also implies the existence of hemodynamically significant RAS (>60-75% of the lumen).
It is important to understand that the criteria for interpreting a result as being positive depend upon the tracer used. If DTPA is used, there should be a change in split function if RVHT is present (since DTPA is dependent upon glomerular filtration rate [GFR] for uptake, the initial uptake in the affected kidney will be decreased). If MAG3 is used, split function will usually not change, but there will be an increase in cortical retention (usually measured as 20 minute to maximum ratio) in the affected kidney. This is because initial MAG3 uptake is primarily dependent upon tubular secretion rather than GFR. However, later clearance of MAG3 is dependent upon GFR (therefore, decreased excretion is the primary finding). Rarely, the split function will change when MAG3 is used in cases of severe RVHT.
Preliminary data suggest that aspirin renography may be as sensitive as captopril renography for detecting RAS. Considering that, compared with captopril, aspirin reduces renal blood flow and thus tubular tracer delivery in poststenotic kidneys, aspirin renography is expected to be more useful, particularly if tubular tracers are used. [30, 31, 32, 33, 34]
Angiographic severity of RAS does not determine the response to revascularization. Renal artery perfusion measured using quantitative PET perfusion imaging shows no change following revascularization. Although, renal perfusion correlates inversely with the degree of RAS in patients with renovascular disease. It has been suggested that this may be due to effects of renal microvascular disease. 
Degree of confidence
Standard renography with131 I-labeled OIH has low specificity and low sensitivity in the diagnosis of RAS.
For RAS greater than 50%, Tc-MAG3 captopril renography has a sensitivity of 90%, a specificity of 91%, a positive predictive value of 70%, and a negative predictive value of 97%.
Data reported by Imanishi et al suggest that123 I-labeled OIH or MAG3 renography is more sensitive for the diagnosis of unilateral RVHT when aspirin is given.  Although Maini et al found that aspirin renography is superior to captopril renography,  results from van de Ven et al show that, for the identification of RAS, the usefulness of aspirin renography equals, but does not surpass, that of captopril renography. 
With standard131 I-labeled OIH radionuclide renography, false-positive results may occur with all conditions that cause unilateral reduction in blood flow. These conditions include chronic pyelonephritis, renal outlet obstruction, renal vein thrombosis, compression of the renal hilum, perirenal abscess, perirenal hematoma, and ptosis of the kidney.
In patients with RVHT, a captopril renogram may yield false-negative results after the long-term administration of captopril despite adequately maintained blood pressure. Therefore, where possible, ACE inhibitors should be discontinued before captopril renography. Overhydration may lead to a false-negative result, and underhydration may lead to a false-positive result. Bilateral RAS may be difficult to diagnose. In patients with poor renal function, examinations are nondiagnostic. A small, asymmetrical kidney with poor function is often unresponsive to a captopril renogram.
Conventional angiography remains the criterion standard for the detection of RAS, although CTA and MRA are increasingly being used. The severity of the stenosis and the presence of collateral circulation to the kidney may be assessed to determine the hemodynamic significance of RAS. Lesions occluding more than 50% of the diameter of the artery are considered significant. The angiographic and the nephrographic phases can be evaluated; the latter may better depict ischemic changes. (See the image below.)
Epinephrine may further restrict blood flow to the kidneys and make the collateral circulation more obvious. Generally, flush aortography suffices for mainstem RAS, but if branch stenosis is suspected, selective renal angiography may better define the lesion. DSA does not address the hemodynamic significance of RAS.
RAS caused by AD generally affects the middle and distal renal artery in 79% of the patients, affects a branch renal artery in 4%, or affects a combination of the 2 in 17%. MFP is bilateral in approximately 65% of cases; the left-to-right ratio is 4:1.
Degree of confidence
Renal angiography remains the criterion standard in the diagnosis of RAS. Angiography is essential when renovascular intervention is contemplated. The angiographic measurement of the size of RAS—an important parameter in assessing the significance of RAS—is inaccurate. Angiography provides only anatomic information; it does not enable the assessment of blood flow through the stenosis.
The right renal artery may originate slightly anterior to the coronal plane. Supplemental renal arteries may be problematic for the angiographer because they may be difficult to find and the catheter tip may obstruct the orifice. The origin of the renal arteries may vary; these arteries may arise from D11 down to the iliac vessels. Furthermore, supplemental branches may arise from visceral arteries.
On DSA images, artifact from moving structures, such as occurs with peristalsis, may be mistaken for RAS. Standing waves may also be confused with RAS.