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Renal Artery Imaging and Physiologic Testing

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Renal Artery Imaging                                                                                 128
and Physiologic Testing
JOSHUA W. BERNHEIM, MD
K. CRAIG KENT, MD


                                                                 regarding surgical or endovascular treatments are based in
■     OVERVIEW




                                                                                                                                  XIX
                                                                 part on the arteriographic appearance of the lesion. An
Renal artery stenosis (RAS) is the most common cause of          understanding of angiographic techniques for evaluation of
secondary hypertension; its prevalence in patients with          the renal arteries is crucial.
hypertension is estimated to range from 1% to 5%.1-5 In
patients with associated atherosclerosis in other vascular
beds, the prevalence may be significantly higher.6 Harding
                                                                 Technique




                                                                                                                                  Section
and associates7 studied the renal arteries in 1235 patients at   Arteriography can be performed with film-screen or digital
the time of coronary angiography and found a 30% inci-           subtraction techniques. In film-screen arteriography, mul-
dence of renal artery disease. In most cases, atherosclerosis    tiple sequential x-ray images are recorded on 14 × 14 inch
or fibromuscular dysplasia is the cause. There has been           film during the intra-arterial injection of contrast material.
increased focus on the diagnosis and treatment of renovas-       The images are reviewed after the film is developed. This
cular disease because this form of hypertension is poten-        approach is rarely used now. With digital subtraction angi-
tially curable. Control of hypertension has been associated      ography (DSA), multiple sequential fluoroscopic images
with a reduction in patient morbidity and mortality.             acquired by an image intensifier are electronically converted
    Owing to the advent of multiple new antihypertensive         to digital form and stored. An image obtained before con-
agents and the aging of the population, patients with athero-    trast injection, the mask, is electronically subtracted from
sclerotic renal artery stenosis (RAS) are presenting later in    images containing contrast material. Only the contrast
the course of their disease and with more advanced renal         material is visualized. The images are displayed imme-
dysfunction. This trend has increased the association of         diately on a 1024 × 1024 matrix screen for review. The DSA
ischemic nephropathy and RAS. It is estimated from an-           images can be modified via the computer and stored on
giographic studies that ischemic nephropathy may be a con-       computer disk or printed.
tributing factor in 43% of patients referred for dialysis or         DSA is sensitive to motion artifact because it involves
renal transplantation.8-13                                       the subtraction of one image from another. Any movement
    It has become crucial to identify accurate methods for       between images degrades image quality. Patient cooperation
diagnosing RAS. Although contrast angiography remains            is necessary, and carefully titrated conscious sedation is
the “gold standard,” because of its invasiveness and             often helpful. For patients with large amounts of bowel gas,
attendant risks, it is not an appropriate screening test for     the intravenous administration of glucagon (0.5 to 1 mg)
all patients thought to have renovascular hypertension or        before image acquisition also improves evaluation of the
ischemic nephropathy. Consequently, many noninvasive             abdominal aorta and its branches by decreasing peristalsis.
modalities have been developed that can be used to evaluate      Small amounts of movement usually can be compensated
this disease process. The noninvasive tests can be divided       for by manually shifting the subtracted mask image relative
into tests that rely on an evaluation of the physiologic         to the contrast-enhanced images.
sequelae of renovascular disease (e.g., captopril test,              Evaluation of the renal arteries usually begins with an
captopril scintigraphy, renal vein renins) and tests that        aortic injection of contrast material. A 5F multiple side-hole
directly image the renal artery (duplex ultrasonography,         catheter is placed into the aorta through a femoral or
magnetic resonance angiography [MRA], and sequential             brachial artery approach14 using a modified Seldinger
helical computed tomography [spiral CT]). This chapter           technique.15 Contrast material is injected with an automatic
reviews and discusses the current knowledge of available         power injector while sequential images are recorded. The
renal artery imaging modalities and physiologic testing.         rate and volume of contrast injection and the rate of image
                                                                 acquisition are determined and specific for each patient.
                                                                 In general, a contrast injection of 10 to 20 mL/sec for 2
■     ARTERIOGRAPHY                                              seconds is usually adequate. Images usually are acquired
Despite technologic advances in noninvasive methods for          at a rate of three per second for 3 to 5 seconds, followed
evaluating the renal arteries, definitive diagnosis of renal      by a rate of one to two images per second for the next
artery pathology continues to depend on visualization of         5 seconds. These images allow assessment of the arterial,
renal artery anatomy with angiographic techniques. After a       the nephrographic, and occasionally the venous phases
diagnosis of renal vascular disease is established, decisions    of flow.
                                                                                                                          1773
1774       Section XIX       THE MANAGEMENT OF RENOVASCULAR DISORDERS


    For optimal visualization of the renal arteries, attention      involves a phosphorus-based image intensifier, which
to several technical details is required. Multiple catheters        detects x-ray beams and creates an analog image, which
have been designed to optimize opacification of the renal            is converted into digital information for display and
arteries during an injection into the aorta.16,17 The catheter      manipulation. Newer systems use a solid-state system that
should be positioned with the side holes at the level of            detects x-rays and creates a digital image directly; this
the renal arteries, usually between the first and second             allows higher resolution with lower radiation dosages and
lumbar vertebrae. Ideally the catheter should be posi-              simplified and more accurate postacquisition image
tioned low enough to avoid filling of the superior mesen-            processing. Three-dimensional DSA is another revolu-
teric artery and its branches, which may overlap and                tionary technique in which the tube makes a single rotation
obscure the renal arteries. The number of renal arteries            around the area of interest before contrast administration,
is highly variable; multiple arteries supplying a single            resulting in the acquisition of a mask. A second revolution is
kidney are seen in 20% to 30% of patients.18-20 The right           performed that coincides with an injection of intra-arterial
renal artery usually arises cephalad to the left. The right renal   contrast material. The mask is subtracted from the contrast
artery usually arises from the anterolateral surface of             image, and three-dimensional reconstructions are created.
the aorta, whereas the left arises from the posterolateral          This technique combines the three-dimensional capabili-
surface.18,21,22 When imaged from an anteroposterior projec-        ties of MRA and CT angiography with the higher resolu-
tion, the proximal renal arteries can be obscured by overlap        tion of DSA. A turn of the tube can take 4 seconds, and two
with the contrast-filled aorta.                                      revolutions are required to obtain an image, so motion
    Because of variability in the number and origins of the         artifact is a potential problem. In addition, the arteries to
renal arteries, many studies have attempted to establish the        be imaged need to be opacified for an entire 4-second
optimal rotational projection for acquiring images.23-27 Most       revolution, necessitating injection of larger volumes of
often, images are acquired in anteroposterior and shallow           contrast material. The benefit of these new technologies is
left anterior oblique projections. Verschuyl and coworkers23        expected to become more evident as they are introduced into
performed a detailed analysis of the angles at which the            clinical practice over the next few years.
renal arteries originate from the aorta using axial images
from CT scans. They found that a 15- to 20-degree left
anterior oblique projection most frequently showed the              Complications of Arteriography
origins of the renal arteries without overlap of the contrast-      The risks of aortography and selective renal arteriography
filled aorta. The next most useful projections were antero-          can be substantial and may include complications related to
posterior, followed by a 40-degree left anterior oblique            the arterial puncture (e.g., hematoma, pseudoaneurysm),
view.24 A projection error of 10 degrees was sufficient to           contrast-induced nephropathy, and cholesterol embolization.
obscure a significant length of the renal artery. As non-            These risks are more prevalent when arteriography is
invasive imaging modalities have gained popularity to               performed in patients with advanced atherosclerosis, severe
screen for disease of the renal arteries, cross-sectional           hypertension, or renal insufficiency,35 all frequent comor-
imaging is increasingly available before arteriography.             bidities with RAS. The prevalence of these complications in
Careful evaluation of noninvasive images often allows a             this specific patient group is not well understood because
prediction of the precise projection that would best depict         large published studies of conventional angiography
the renal arteries. This approach can save unnecessary              generally include “uncomplicated patients” who have only
injections of contrast material in patients who are already at      renovascular hypertension and normal renal function. The
high risk for contrast nephropathy.                                 complications of angiography are often insidious and difficult
    Aortography with optimized technique usually provides           to assess accurately, especially retrospectively. Among 2374
adequate evaluation of the main renal arteries and the              patients who underwent contrast angiography as part of the
segmental and subsegmental branches.28-31 In some cases,            Cooperative Study of Renovascular Hypertension,36 a
selective catheterization of the renal arteries32 allows better     fatality rate of 0.11%, a nonfatal major complication rate of
visualization of the orifice and distal branches without             1.2%, and a minor complication rate of 2.7% were observed.
overlap from the aorta or other vessels. Catheterization of         The authors of this study relied on self-reporting by
the renal artery usually is performed with a preshaped              radiologists at many different centers. The subjects were
Cobra, Omni Selective, or Simmons (all three manufactured           principally patients who had normal renal function.
by Angio Dynamics, Queensbury, NY) type of catheter, with              Contrast nephropathy is discussed in detail in Chapter 58.
hand injection of contrast material or power injection of           The incidence of contrast-induced nephropathy varies signi-
3 to 6 mL of contrast material per second for 1 to 2 seconds.       ficantly and has been reported to range from 0 to 7%, with
Selective renal arteriography limits the total volume of            the largest studies reporting an average incidence of 3%.37
contrast material used for imaging in renal vessels in              Risk factors for the development of acute contrast-induced
multiple obliquities. Selective arteriography also provides         nephrotoxicity include dehydration,38renal insufficiency,39-43
the opportunity to evaluate the hemodynamic effects of a            and diabetes mellitus.41,43,44 In some studies, the combination
stenosis. This evaluation can be accomplished with direct           of diabetes and renal insufficiency has been shown to increase
pressure measurements proximal and distal to the lesion.33,34       the risk to 20% to 50% depending on the degree of pre-
The ability to measure pressures across a RAS is valuable           existing renal dysfunction.45 Diabetic patients with renal
and is not available with noninvasive imaging modalities.           insufficiency are at highest risk. In patients who do not have
    Numerous new technologies currently are being inves-            risk factors, acute contrast-induced nephrotoxicity is usually
tigated and warrant mention. Traditional image acquisition          transient.41,42,46-49
                                                       C H A P T E R 128   Renal Artery Imaging and Physiologic Testing      1775


   Atheroembolism is an increasingly recognized com-               have validated the efficacy of N-acetyl cysteine.64-67 The
plication of renal arteriography. It tends to be under-            mechanism of N-acetyl cysteine’s protective effect is poorly
diagnosed because it is an insidious disorder that is difficult     understood but may be related to increased nitric oxide
to identify with certainty without performing a biopsy.50          production and decreased oxidative stress.68 Although
Only the most fulminant cases are recognized clinically.           conflicting studies in the literature show no benefit,69-72 the
Although clinical studies generally have reported a low            benign nature and low cost of this agent have led to its
incidence (1.4% in one large series51), autopsy studies found      widespread and liberal application.
evidence of atheroemboli in 25% to 30% of patients who                 Despite the failure of dopamine infusion to prevent
died within 6 months after cardiac catheterization or              contrast-induced nephropathy,73,74 Bakris and colleagues75
aortography.52 Patients with widespread atherosclerotic            showed in a dog model that fenoldopam mesylate, a selec-
disease and preexisting renal insufficiency—precisely the           tive dopamine-1 receptor antagonist, prevented the decrease
population at risk for ischemic nephropathy—are the                in glomerular filtration rate (GFR) and renal blood flow
patients who are most susceptible to atheroembolism.               associated with intravenous contrast injection. In 2001,
   Although conventional angiography can detect the                Hunter and coworkers76 reported a series of 29 patients
anatomic presence of a renal artery lesion, it does not pro-       with diabetes and renal insufficiency who received fenold-
vide data on the physiologic or hemodynamic significance.           opam before angiography. Only one patient experienced an
Also, because conventional angiography provides only a             increase in creatinine. Tumlin and colleagues,77 in a
two-dimensional image and does not allow imaging of                randomized trial, showed a significant benefit to fenoldopam
the renal artery in multiple planes, it can be difficult to         infusion. Other studies, including a randomized, controlled
determine the precise degree of stenosis. Even when                trial involving 315 patients with baseline renal insufficiency
multiple views are obtained, it can be difficult to identify        (CONTRAST investigators),78 have failed to show benefit,
accurately the origin of a tortuous renal artery that arises       however. Because use of fenoldopam is more involved and
from a severely diseased aorta. Despite these limitations, if      costlier than N-acetyl cysteine, it has not gained popularity.
the index of suspicion for RAS is high and the patient has         Larger randomized, multicenter trials are needed to confirm
reasonably acceptable renal function, it may be appropriate        its benefit.
in certain circumstances to proceed directly to conventional           For patients at significant risk for contrast-induced
angiography without performing a noninvasive study.                nephrotoxicity or who have an allergy to iodinated contrast
                                                                   material, exposure can be drastically limited or entirely
Contrast Material                                                  avoided if carbon dioxide (CO2) is used as the contrast
                                                                   agent. Intravascular CO2 was first used for the diagnosis of
Intravascular administration of contrast material has been         pericardial effusions in the 1950s.79 Extensive animal testing
established as a risk factor for the development of renal          established its intravascular use to be safe, even with the
insufficiency.53,54 Factors that appear to increase the risk of     administration of massive volumes.80,81 CO2 passes rapidly
renal dysfunction include use of high volumes of contrast          through the capillary bed and is absorbed or routed through
material55-59 and use of high-osmolar contrast.60 Iodixanol,       the venous system back to the heart and eliminated through
an isosmolar contrast agent available since the late 1990s,        the lungs.82 Repeated, large-volume CO2 injections made at
may provide reduced risk.61 There also may be an advantage         frequent intervals can produce a “vapor lock,” which rarely
to non-ionic contrast material. In a prospective, randomized,      can cause transient ischemia. In addition, injection of CO2
double-blinded, multicenter trial involving 1196 patients          into the intracranial circulation has never been proved
undergoing cardiac angiography, Rudnick and colleagues39           safe in humans, and its use in animals has resulted in
found that the use of a non-ionic contrast agent did not           unexplained complications.83 It also is crucial to prevent
influence the incidence of renal failure in the study popu-         room air from entering the injection system to avoid an air
lation as a whole. In patients with the highest risk (i.e.,        embolus. Several technical factors become important when
patients with renal insufficiency with or without diabetes),        using CO2. Ideally a dedicated CO2 injector should be
the use of non-ionic contrast was beneficial. Patients with         used, but some authors have been successful in creating
renal insufficiency receiving diatrizoate (ionic) were 3.3          “homemade” systems, using great care to avoid contami-
times more likely to develop acute nephrotoxicity compared         nation with air and overinjection.84 Ample time between
with patients receiving iohexol (non-ionic).                       injections should be allowed for clearance of the bolus—
    Several measures to prevent acute contrast-induced             usually 2 to 3 minutes to prevent vapor lock. Volumes of 25
nephrotoxicity have been evaluated, including pretreat-            to 80 mL over 1 second are usually adequate to image the
ment with mannitol, diuretics, calcium channel blockers,           abdominal aorta. An attempt should be made to keep total
theophylline, or dopamine (see Chapter 58). No significant          volumes less than 400 mL. Elevation of the kidney of
benefit of any of these agents over simple infusion of saline       interest facilitates filling of the vessel owing to the buoyancy
has been shown yet.62 Two agents that have received a great        of the gas. Movement of bowel gas, a bigger problem than
deal of attention are N-acetyl cysteine and fenoldopam. In a       with standard angiography, can be minimized by the
landmark study in 2000, Tepel and coworkers63 evaluated            administration of an antiperistaltic agent.
N-acetyl cysteine in a randomized, prospective, placebo-               It is widely believed that gas entry into the mesenteric
controlled study comprising 83 patients with chronic renal         circulation causes the abdominal bloating, pressure, and
insufficiency. Two percent of patients in the treatment arm         cramps that patients sometimes experience during injec-
developed a significant increase in serum creatinine versus         tions. End-hole catheters may produce a smoother bolus
21% of the control patients. Several subsequent studies            than flush catheters when using CO2 because they do not
1776      Section XIX      THE MANAGEMENT OF RENOVASCULAR DISORDERS


break up the “bubble.” Stacking of consecutive images is         imaging modalities realize that, under some circumstances
often helpful because of the rapid transit of the gaseous        (particularly because of the three-dimensional capabilities
contrast in the arterial system. CO2 results in images with      of many of these techniques), these studies may be more
lower resolution than with contrast angiography; however,        revealing and accurate than contrast angiography. The
with experience CO2 can be used effectively for renal artery     ultimate test of any imaging technique designed to screen
imaging.85-93 If necessary, supplemental views with a limited    for RAS is its capability of identifying which patients would
volume of low-osmolar iodinated contrast material can be         respond clinically to renal artery revascularization.
acquired after the optimal projection has been determined            It is difficult to obtain consensus on the diagnostic
with CO2.85,88,94,95 In this manner, optimal high-quality        accuracy and utility of the various noninvasive methods
images of the renal arteries can be obtained with 2 to 10 mL     of renal artery imaging. For each modality, investigators
of contrast material. Angiograms of diagnostic quality are       have employed a variety of approaches and techniques.
obtained in 79% to 95% of patients, with sensitivity and         Compounding this problem is the fact that the parameters of
specificity of 83% and 99%.96,97                                  reporting often vary from one institution to another. In many
   Another potential alternate contrast material is gado-        studies, the threshold for determining significant RAS is
pentetate dimeglumine (gadolinium), which is the contrast        50%. Most clinicians reserve intervention for renal artery
agent routinely used during magnetic resonance imaging           lesions that are greater than 70%, however. Finally, patients
(MRI). Gadopentetate dimeglumine does not pose a risk of         entered into these studies are almost exclusively patients
nephrotoxicity,98-100 but it costs approximately four times      who have been referred for angiography. This “selected”
more than low-osmolar iodinated contrast material. Adverse       population tends to have a high prevalence of renal artery
reactions have been reported and include nausea, headache,       disease. It is difficult to extrapolate from the results of these
and dizziness in 3% of patients and signs of asymptomatic        studies to a patient cohort that is being screened, because
hemolysis in 1% to 3%.101,102 These side effects are minor,      disease is much less prevalent in the latter group.
however, and often self-limited. Also, hypocalcemia has
been observed in patients who have received large quantities
of gadolinium. It is recommended that doses not exceed           Duplex Ultrasonography
0.25 mmol/kg because larger doses have not been proved           Duplex ultrasonography is the imaging modality that has
safe.103-105 Ailawadi and colleagues101 reported adequate        been most intensively investigated. Duplex ultrasonography
visualization in 38 renal arteries that were evaluated only      combines direct visualization of the renal artery via B-mode
with gadolinium. There were no adverse effects on renal          imaging with Doppler measurement of the velocity of blood
function in any of the patients studied. The major obstacles     flow. This combination affords anatomic evaluation and
to the widespread adoption of gadolinium-based agents in         hemodynamic assessment of the renal vessels.106 Duplex
renal artery imaging are lower contrast resolution and the       ultrasonography also allows simultaneous measurement of
high cost of these agents. In high-risk patients, gadolinium     kidney size. Resistive indices of the segmental arteries can
remains an effective alternative to iodinated contrast           be measured by duplex scanning; these values also may be
material.                                                        useful in predicting response to renal revascularization.

                                                                 Technical Considerations
■      NONINVASIVE RENAL
                                                                 Because of the depth of the renal arteries and their location
       ARTERY IMAGING                                            in the retroperitoneum, it is difficult with B-mode imaging
An ideal noninvasive imaging study would serve as an             to assess directly the luminal anatomy along the entire
accurate screening tool for RAS and a means for delineat-        length of the renal artery and its branches. Instead, ultra-
ing renal anatomy before arterial reconstruction. Other          sound is used to locate the main renal artery. After the renal
attributes of the ideal imaging technique are minimal            artery is identified, Doppler measurements can be sampled
expense, excellent accuracy, good reproducibility, and low       sequentially at regular intervals along its length and in
complication rate. In recent years, numerous, less invasive      the kidney itself. These measurements are processed into
renal artery imaging strategies have been evaluated. Each        spectral velocity waveforms using fast Fourier transform
has its advantages and disadvantages, but overall these          analysis (Fig. 128-1). A significant stenosis is indicated by
studies are safer than conventional angiography. As opposed      an increase in velocity, which reflects acceleration of the
to the traditional screening tests that rely on physiologic      blood as it crosses the area of narrowing. Alternatively, with
criteria (i.e., captopril test, radionuclide renography, renal   indirect techniques, a proximal stenosis can be inferred from
vein renins), noninvasive imaging studies require no             an abnormal Doppler waveform in the more distal segmental
preprocedural adjustments in a patient’s medication or diet.     arteries of the kidney.
Also, their accuracy is not diminished by renal insufficiency.       The main renal artery should be examined with the
Noninvasive imaging techniques also can supply detailed          patient fasting to avoid interference from overlying bowel
anatomic information that potentially might obviate the          gas. A low-frequency transducer (range 2 to 3.5 Hz) should
need for preoperative angiography.                               be used, and Doppler-shifted signals should be obtained at
    In all investigations of noninvasive imaging modalities to   less than a 60-degree angle to the artery. It is essential to
date, contrast angiography has been used as the standard of      survey the entire renal artery, including the proximal,
comparison. Because of the previously mentioned limita-          middle, and distal portions. If the artery is not examined
tions of conventional angiography, there is no true standard.    carefully throughout its length, significant stenoses, espe-
Clinicians who have worked extensively with noninvasive          cially stenoses that are the consequence of fibromuscular
                                                       C H A P T E R 128   Renal Artery Imaging and Physiologic Testing           1777


                                                                                                  FIGURE 128-1 Duplex ultrasound
                                                                                                  spectral analysis and corresponding
                                                                                                  angiogram for a patient with unilat-
                                                                                                  eral renal artery stenosis. Arrows A,
                                                                                                  B, and C indicate the approximate
                                                                                                  sites along the renal artery where the
                                                                                                  Doppler measurements were obtained.




disease (which can be focal or distal or both), may be             main RAS.114-119 The exact site of the renal artery lesion can
missed. The examination can be performed without discon-           be accurately ascertained in 80% to 95% of patients.153
tinuing antihypertensive medications and is appropriate               Other investigators have been unable to duplicate these
even for patients who have advanced renal insufficiency.            excellent results. Sensitivities of 0 and rates of inadequate
   Numerous parameters have been reported for the iden-            examinations of 40% have been reported.120-123 There are
tification of a hemodynamically significant main RAS.107-111         many limitations to duplex ultrasonography that may account
The most widely accepted criteria are (1) a ratio of the peak      for these variations in accuracy. Frequently encountered
systolic velocity in the renal artery to the peak systolic         technical difficulties include inability to identify the main
velocity in the adjacent aorta greater than 3.5:1 and (2) a        renal artery because of overlying fat or bowel gas, difficulty
peak systolic velocity in the renal artery greater than 180        interrogating the entire length of the renal artery, and
to 200 cm/sec in association with post-stenotic turbulence.        inability to obtain an optimal angle of insonation. Traditional
In numerous studies, these criteria have correlated with           duplex ultrasonography techniques do not allow accurate
an “angiographic stenosis” of greater than 60%. An end-            identification of accessory renal arteries,120,124 which may
diastolic velocity (EDV) 150 cm/sec or greater may signify         be present in 30% of kidneys.125 This information may be
an 80% or greater angiographic stenosis.112 The absence of         clinically important because stenosis of an accessory renal
a flow signal in the renal artery signifies an occlusion.            artery is frequently the cause of reversible renovascular
   Direct interrogation of the renal arteries is a labor-          hypertension.
intensive and time-consuming undertaking that requires a              Numerous attempts have been made to overcome these
dedicated and experienced technologist and a cooperative           limitations. The most studied of these is the method of
patient. In centers where this test has been developed and         indirect Doppler evaluation of the distal renal arterial tree.
studied extensively, excellent results have been obtained. In      Through a flank approach, segmental waveforms are
one of the earliest large studies, Hansen and coworkers113         obtained at the hilum and the upper, middle, and lower poles
evaluated 74 consecutive patients with duplex ultrasonog-          of the kidney. The presence of a more proximal high-
raphy and conventional angiography. Duplex ultrasonography         grade renal artery lesion is inferred when a tardus or
predicted the presence of a main RAS greater than 60% with         parvus waveform is observed in the distal vessels (Fig.
a sensitivity of 93% and specificity of 98% when only               128-2). The hemodynamic significance of these lesions is
kidneys with single renal arteries were evaluated. When            determined by evaluating the acceleration time (normal
patients with multiple renal arteries also were considered,        value < 0.07 second), acceleration index (normal value
the sensitivity decreased to 88%, although the specificity          > 3 m/sec2), and waveform pattern recognition. Many
remained high (99%). Other centers also have reported              published series have shown this technique to have excel-
sensitivities that range from 84% to 98% and specificities of       lent accuracy in predicting angiographically significant
90% to 98% for the detection of angiographically significant        RAS.126-130 Radermacher and associates126 used this tech-
1778        Section XIX         THE MANAGEMENT OF RENOVASCULAR DISORDERS




 A                                                                                                                                                 B




   C                                                                                                                                             D

FIGURE 128-2 Waveforms obtained from indirect duplex ultrasound analysis of the distal renal arterial tree. A, Graphic representation of a normal
waveform. B, Graphic representation of an abnormal waveform that would indicate the presence of significant renal artery stenosis. C, Waveform represents
a normal study; the acceleration time (AT) was calculated to be 0.025 sec (normal < 0.07 sec), and the acceleration index (AI) was 7.51 m/sec2 (normal
>3 m/sec2). D, Waveform represents a highly abnormal study suggestive of renal artery stenosis with an AT of 0.242 sec and AI of 2.46 m/sec2.




nique as an adjunct when direct evaluation of the renal                       nephrosclerosis or glomerulosclerosis. It is hypothesized
artery failed or was difficult. With this approach, these                      that these kidneys are unlikely to benefit from revascu-
investigators eliminated technical failures with a resultant                  larization. Radermacher and associates131 reported on 131
decrease in the time required to perform the test. In other                   patients who underwent successful renal revasculariza-
studies using indirect Doppler techniques, a measurement                      tion. Patients who had a RI greater than 0.8 were highly
called the resistive index (RI) has been used as a criterion for              unlikely to benefit from surgery or angioplasty. Such
RAS (normal RI < 0.70). This value, which estimates the                       patients experienced less improvement in blood pressure
state of renal arterial resistance, is defined as follows:                     and more frequent deterioration of renal function. In
                                                                              contrast, most patients with lower RIs benefited, with 94%
           Peak systolic shift minimum diastolic shift                        experiencing a decline in blood pressure and only 3%
     RI    ———————————————————–
                         Peak systolic shift                                  progressing to dialysis.131
                                                                                  Indirect techniques have many potential advantages over
   This measurement has decreased specificity because it                       direct interrogation of the renal artery. Segmental waveform
also can be elevated in the presence of medical renal disease,                analysis is much less time-consuming, and the results may
decreased cardiac output, or perinephric or subcapsular                       be less dependent on operator experience than the results
fluid collections. Others have used the RI not as a tool to                    derived from direct renal artery interrogation. Because the
determine the presence of RAS, but as a predictor of                          examination is performed from a lateral approach, adequate
response to renal revascularization. The higher the RI, the                   data can be obtained even in obese patients and patients
more likely the kidney is affected by severe underlying                       who have excessive bowel gas. Accessory renal artery
                                                        C H A P T E R 128   Renal Artery Imaging and Physiologic Testing     1779


disease can be identified by a damped waveform isolated to              Duplex ultrasonography also has been used intraopera-
a kidney pole.132                                                   tively to detect and allow correction of technical problems
   Disadvantages of the indirect technique include the              that occasionally complicate renal artery bypass or endar-
inability to distinguish a severe stenosis from an obstruction      terectomy.125,141 The superficial location of the transplanted
and the lack of information regarding the exact location of a       kidney also makes this study well suited for investigating
stenotic lesion. The systolic features of renal artery spectral     suspected transplant RAS.142-144 Finally, duplex ultraso-
analysis are affected by increased renovascular resistance          nography has been used to evaluate the results and long-
(see Fig. 128-1). Increased resistance may change distal            term patency after percutaneous renal angioplasty or
renal artery acceleration time or acceleration index in             stenting or both.145,146
40% of hemodynamically significant stenoses associated                  One drawback of duplex ultrasonography is that it does
with renal insufficiency.107,113 In preliminary studies, several     not provide the necessary anatomic information that
investigators have shown that the sensitivity of this               would allow surgical intervention without first obtaining a
technique can be enhanced by using an ultrasound contrast           contrast angiogram. Duplex ultrasonography is accurate in
agent or by administration of captopril before the                  detecting celiac artery stenoses,147 however, and this
study.133-135 Many centers, including our own, have begun to        information may be useful in patients with severely diseased
perform direct examination of the renal arteries and indirect       aortas when hepatorenal or splenorenal bypass is being
segmental waveform analysis routinely.                              considered.
                                                                       Renal artery duplex ultrasonography is an excellent
                                                                    screening test for hemodynamically significant RAS in
Emerging Strategies                                                 centers where the appropriate technical expertise is
Other strategies have been employed to improve the accu-            available. Of the various alternatives for noninvasive
racy of main renal artery interrogation. In a few preliminary       imaging, duplex ultrasonography is the least expensive.
studies, intravenous contrast agents significantly enhanced          Adding indirect techniques and using contrast agents may
the diagnostic accuracy of duplex ultrasonography. These            increase its accuracy and reproducibility further, which
agents may decrease examination time and increase                   would make it a more widely acceptable study for RAS
accuracy by allowing (1) easier identification of the main           screening. In addition, measurement of the RI has shown
renal artery and (2) detection of a larger percentage of            promise in predicting which patients will respond to
accessory renal arteries. Claudon and associates136 reported        revascularization.
that intravenous administration of SH U 508A (Levovist)
before duplex examination increased the number of
technically successful studies from 64% to 84%. Contrast            Magnetic Resonance Angiography
administration also seemed to increase accuracy, with 70%           MRA also has been extensively evaluated as a method for
of enhanced scans correlating with angiography versus only          noninvasively evaluating RAS. MRA can show vascular
52% of nonenhanced studies. Although the overall accuracy           anatomy and generate an image that is similar in appearance
of duplex ultrasonography in this trial was less than what          to that obtained by conventional angiography (Fig. 128-3).
has been reported in other single-institution studies, these        In contrast to conventional angiography, however, MRA
results may be representative of what can be achieved               does not require arterial puncture or nephrotoxic agents.
at centers without special expertise in renal duplex ultra-         In contrast to the traditional physiologic studies for
sonography. At least in this setting, contrast agents seem to       RAS, there is no need to discontinue antihypertensive
improve accuracy. Although ultrasound contrast agents may           medications, which interfere with the renin-angiotensin
prove to be adjuncts in the evaluation of RAS by duplex             system, and the accuracy of MRA does not diminish
ultrasonography, larger, more thorough studies must be              because of renal dysfunction. The similarity of the images
conducted to determine their definitive role.                        generated by MRA and by conventional angiography
                                                                    increases the comfort level of clinicians. There are
                                                                    significant differences in these images, however, and the
Other Clinical Applications                                         interpretation of renal MRA requires specific expertise and
In addition to being a screening tool, duplex ultraso-              experience.
nography has proved useful for numerous other clinical                  The physics of MRA is complex, and a complete descrip-
applications. Because it is noninvasive and can assess              tion of this technique is beyond the scope of this chapter.
kidney size and the degree of stenosis, duplex ultraso-             The clinician should have a basic understanding of the
nography has become the procedure of choice for following           fundamental principles that underlie MRA, however, to
patients with documented renal artery disease who are being         recognize its advantages and limitations. Numerous differ-
treated medically.137,138 Duplex ultrasonography also can           ent MRA techniques can be used to image the renal
be used to monitor long-term patency after surgical recon-          arteries.148,149 In early studies, two imaging techniques were
struction of the renal arteries. Studies have confirmed that a       employed: time of flight (TOF) and phase contrast (PC).
normal postoperative duplex scan is highly predictive of a          With both, protons in tissue and blood are charged when the
patent bypass graft.139,140 Because of their size and position      body is exposed to a magnetic field. The protons emit a
adjacent to the abdominal aorta, aortorenal grafts are often        signal that is registered as a visual image. TOF imaging
easier to assess than native renal arteries. Hepatorenal,           relies on flow-related enhancement to image the renal
splenorenal, and iliorenal bypasses are more difficult to            arteries. With multiple magnetic pulses delivered at short
study, but a skilled technician often can successfully scan         intervals, stationary protons are “saturated” so that they no
even these.                                                         longer yield signal, whereas moving protons yield maximal
1780        Section XIX        THE MANAGEMENT OF RENOVASCULAR DISORDERS




 A                                                                                                                                          B

FIGURE 128-3 A, Three-dimensional gadolinium-enhanced magnetic resonance angiogram shows severe left renal artery stenosis. B, The corresponding
conventional contrast angiogram from the same patient.




signal. PC imaging relies on the differences in phase shift               gadolinium clearance, and detection of turbulent flow
between moving and stationary protons.                                    resulting in signal loss in nonenhanced studies all may be
    More recently, a third approach called three-dimensional              used to detect the physiologic sequelae of RAS.151-155 The
gadolinium-enhanced MRA has become the standard of care                   clinical applicability of these techniques awaits further
in renal artery MRI. With this technique, many of the                     investigation.
shortcomings of TOF and PC MRA have been overcome,
including (1) saturation effects that can make vessels with
relatively slow flow appear stenotic; (2) turbulence-induced               Clinical Experience
signal loss, which results in overestimation of stenoses; and             Using a breath-holding, three-dimensional gadolinium-
(3) long imaging times. Rather than image individual                      enhanced method, DeCobelli and coworkers156 achieved
protons in flowing blood, this method allows direct                        100% sensitivity and 97% specificity for RAS greater than
visualization of the contrast agent filling the lumen similar              50%. Using these same techniques, they correctly identified
to conventional angiography. When this technique was                      significantly more accessory renal arteries than could be
initially developed, long acquisition times (approximately                found using a PC technique. Many other investigators also
2 to 3 minutes) were necessary; however, distal and acces-                have reported excellent results with three-dimensional
sory arteries could not be assessed accurately owing to                   gadolinium-enhanced MRA.157-162 Hany and coworkers163
respiration artifact. More recently, rapid bolus injections               reported the largest series to date, which included a
used with suspended respiration have produced slightly                    comparison of 103 patients who underwent gadolinium-
poorer resolution, but less pronounced respiratory artifact.              enhanced MRA and contrast angiography. Using this tech-
    Data from MRA are compiled initially as multiple, thin,               nique, these investigators reported a sensitivity and speci-
contiguous cross-sectional slices. The slices are converted               ficity of 93% and 90%. Using a combination of anatomic
into a three-dimensional data set, which can be used to                   images from gadolinium-enhanced MRA and physiologic
create projections in any orientation that look like conven-              data from cine PC MRI, Schoenberg and colleagues164 also
tional angiograms. The most commonly used reconstruction                  showed excellent correlation between MRI and digital
technique is called a maximal intensity projection (MIP).150              angiography in the evaluation of RAS.
In contrast to conventional angiography, MRA allows data                     Because of the high degree of accuracy associated with
to be projected in multiple planes (axial, coronal, sagittal,             MRA and its ability to image arterial anatomy, in certain
oblique). This flexibility is particularly useful for inves-               cases surgeons may proceed directly to operation for RAS
tigating the renal ostium and tortuous renal arteries. To                 without preoperative conventional contrast angiography.165
assess the degree of stenosis accurately, it is necessary to              This advantage has become less relevant as angioplasty and
examine the nonreformatted axial images because the                       endoluminal stents have become widely applied to RAS.
reformatting process, although it produces visually satisfy-              MRA remains an important screening test for renal artery
ing images, often can lead to overestimation or underesti-                disease, however. MRA also has been evaluated for
mation of the degree of stenosis.                                         detection of RAS in transplants, although not as thoroughly
    In addition to defining the anatomy, attention has                     as has duplex ultrasonography. Although the accuracy has
focused on the use of MRA to evaluate several physi-                      been satisfactory when MRA is used for this purpose, false-
ologic parameters. PC flow measurements, assessment of                     positive findings occur frequently.166-168 Another potential
                                                                  C H A P T E R 128     Renal Artery Imaging and Physiologic Testing               1781




  A                                                                                                                                                 B

FIGURE 128-4 A, Three-dimensional gadolinium-enhanced magnetic resonance angiogram shows severe ostial accessory renal artery stenosis. B, The
conventional contrast angiogram of the same accessory renal artery reveals only a mild lesion. Pull-back pressures revealed no gradient across the ostium
of this renal artery.




advantage of MRA is its ability to obtain functional and                          The most striking aspect of MRA, as used to detect
anatomic data.169 Several investigators have been able to                      proximal renovascular disease, is its extremely low false-
estimate split renal function accurately with clearance of                     negative rate. In most series, sensitivity is almost 100%,
gadolinium contrast agents using a method similar to con-                      which makes it an excellent screening tool for suspected
ventional radionuclide renography.170-172 Others have used                     ischemic nephropathy secondary to atherosclerotic disease
gated MRI techniques to assess accurately renal blood flow                      of the main renal artery. Because of this high negative
in patients with renal artery disease.173,174 It is also possible              predictive value, a clinician can be confident that with a
to obtain the rates of tissue diffusion and perfusion; both of                 normal MRA study, functionally significant renal artery
these measurements may help to delineate the physiologic                       disease is exceedingly unlikely. Because of its current
significance of RAS.175                                                         tendency to overestimate the degree of stenosis, MRA is
    Although the popularity of MRA for noninvasive                             less accurate than conventional contrast angiography in
imaging is increasing, it has many limitations. False-positive                 defining high-grade RAS; however, MRA technology is
scans are common (Fig. 128-4). MRA has a general                               continually evolving, and the images are expected to
tendency to overestimate the degree of stenosis. Although                      continue to improve.
images may appear strikingly detailed, they do not strictly
correlate with luminal anatomy. Breath-holding, three-
dimensional gadolinium-enhanced MRA is now the MRA
                                                                               Helical (Spiral) Computed Tomography
technique most often used for imaging the renal vasculature.                   Helical CT has emerged as a promising technique for
Although it seems to afford superior resolution of accessory                   identifying RAS. Spiral CT employs a rotating gantry,
and branch renal arteries, few patients with fibromuscular or                   which allows numerous images to be acquired over a
other distal renal artery lesions have been studied. MRA is                    relatively brief time. For arterial imaging, intravenous
not the screening test of choice for patients who may harbor                   iodinated contrast material is injected through a peripheral
such lesions. Three-dimensional gadolinium-enhanced MRA                        vein. After an appropriate delay to allow passage of the
also requires patients to hold their breath for a short time,                  contrast agent into the renal arterial circulation, a series of
which may be difficult for patients with significant cardiac                     thin cuts are obtained throughout the aorta at the level of
or pulmonary disease. Some patients are unable to tolerate                     the renal arteries. Rapid acquisition of data afforded by
the study because of claustrophobia. MRA also is contra-                       spiral CT allows multiple images to be made precisely at
indicated in patients with pacemakers, cerebral aneurysm                       the moment when the contrast medium passes through the
clips, or intraocular metal devices. Neighboring surgical clip                 renal vessels.
artifact can produce signal voids and false-positive studies.                     Many technical variables must be optimized if the renal
Finally, although it is not always evident when reviewing                      arteries are to be imaged adequately by spiral CT.176 Several
published reports, considerable expertise is required to obtain                of these parameters (collimation, table speed, pitch)
high-quality images and proper interpretation.                                 determine the interval at which cuts are acquired. These
1782      Section XIX       THE MANAGEMENT OF RENOVASCULAR DISORDERS


variables are adjusted so that sections are taken at 2- to            Although helical CT has been less widely studied than
3-mm intervals,177 which afford a resolution of approxi-          MRA or duplex ultrasonography, numerous centers with expe-
mately 0.5 mm (whereas that for MRA is 1 to 1.5 mm). It is        rience in helical CT have produced favorable results.179-183
also necessary to adjust the rate of injection and the interval   Wittenberg and coworkers184 prospectively compared helical
between peripheral injection and renal artery imaging.            CT and conventional angiography in 82 consecutive patients
Optimizing both of these timing variables allows maximal          suspected to have renal artery disease. Helical CT detected
enhancement of the renal arteries by contrast medium. If the      stenoses greater than 50% with sensitivity of 96% and
contrast bolus arrives in the renal arteries too early, the       specificity of 99%. Five adrenal masses were incidentally
volume of contrast is inadequate for complete visualization       detected. In 50 patients with suspected renovascular disease,
of the renal vessels. If the bolus arrives after imaging has      Deregi and coworkers185 found helical CT to have sensitivity
begun, contrast returning from the renal vein might obscure       of 100% and specificity of 98% for main renal artery lesions
the renal artery. The importance of precise timing has            more extensive than 50%. The two false-positive results in
led many investigators to administer a test bolus using 15        this study were related to difficulty imaging the right main
to 20 mL of contrast material. Interval imaging over 30           renal artery adjacent to the vena cava. When accessory renal
seconds allows the physician to estimate when contrast            arteries were included in this evaluation, the sensitivity
enhancement of the renal vessels is maximal. Breath holding       decreased to 88%. Kim and associates186 studied 50 patients
longer than 20 seconds is required during image acquisition.      with CT angiography, and conventional CT. These authors
It is essential that patients remain immobile for these studies   reported a 90% sensitivity and a 97% specificity for CT
because motion artifact reduces the quality of the images.        angiography in the detection of RAS greater than 50%.
The entire study takes only 20 to 30 minutes.                         In addition to its great accuracy, other advantages of
    After the raw images are acquired, postprocessing is the      helical CT include the ability to determine renal size,
next step. Initially the data are interpolated into axial         cortical thickness, and, potentially, kidney perfusion.187 It
sections, then reconstructed images are rendered. This            also affords simultaneous evaluation for aortic aneurysms
time-consuming process takes 30 to 90 minutes for an              and adrenal gland anatomy in patients suspected to have
experienced radiologist or technician. Although many              secondary hypertension.188-190 In contrast to MRA, helical
reconstructive techniques exist, the techniques currently         CT can be used to assess the patency of renal arteries that
available on most commercial CT systems are MIP and               have been treated with endoluminal stents.
surface-shaded display (SSD). Images provided by these                The principal drawback of spiral CT for imaging renal
two techniques differ, as does the information they relay.178     arteries is the necessity for iodinated contrast medium. For
MIP is a method wherein the raw data are reconstructed            most studies, 120 to 150 mL of contrast agent is required.
using the maximum-intensity signal along each ray through         This is a quantity significantly greater than that required for
the data set (Fig. 128-5A and B). MIP enhances visual             digital subtraction angiography (15 to 20 mL if selective
distinction between the blood vessel and background tissue.       renal images need not be obtained). For this reason, helical
The images are two-dimensional, however, and depth                CT may not be appropriate for the increasing number of
relationships are not apparent, and overlapping vessels are       patients with renal insufficiency who undergo screening for
not clearly delineated. Displaying multiple MIP images            renal artery disease.
minimizes this problem. SSD has the advantage of three-               Similar to duplex ultrasonography and MRA, helical CT
dimensional representation of anatomic relationship (Fig.         does not produce satisfactory images of accessory renal
128-5C). Depending on the chosen threshold, however, SSD          arteries.177 Although these arteries often can be identified,
can exaggerate stenoses, and surrounding structures can           the extent to which they are diseased is difficult to assess
produce artifacts that obscure arterial anatomy. Generally,       owing to poor resolution. Because branch renal arteries tend
MIP is the more accurate of the two techniques, although          to lie in a single plane, they too are often inadequately
SSD is the more visually “pleasing.” When one is deter-           imaged by helical CT. Even with these limitations, CT may
mining renal artery anatomy and degree of stenosis, images        be more accurate than MRA for detecting lesions related to
from all available modalities should be reviewed. In addition     fibromuscular disease. Other drawbacks of spiral CT include
to the MIP and SSD reconstructions, much information              long postprocessing times, inability to image patients who
can be obtained by examining the original axial data or by        weigh more than 125 kg, and a general tendency to produce
using multiplanar reformats. Such a complete analysis             false-positive results. False-positive images can result from
allows repeated confirmation of the degree of stenosis,            incomplete opacification of the renal arteries secondary to
which improves diagnostic accuracy.                               poor timing of a contrast bolus, overlying calcification, or
    Regardless of which technique is used, the major hin-         artifact from adjacent tissue. Despite these limitations, for
drance of helical CT is arterial calcification. In MIP-            patients with relatively normal renal function and in
formatted images, calcium obscures the vessel lumen.              centers with appropriate experience and expertise, spiral CT
Atherosclerotic disease can be inferred by the presence of        offers an accurate, less invasive assessment of renal artery
calcium, but the degree of stenosis cannot be gauged              anatomy.
accurately. In SSD-formatted images, it is impossible to
differentiate calcium from contrast medium. Calcified
atheromas blend with intraluminal contrast and create
                                                                  ■     FUNCTIONAL STUDIES
the image of a widely patent vessel. Numerous calcium             In 1934, Goldblatt and associates191 made the seminal dis-
suppression techniques have been studied, but they have           covery that constriction of the renal artery in a dog caused
marginal utility.                                                 an elevation in blood pressure proportional to the degree of
                                                                 C H A P T E R 128     Renal Artery Imaging and Physiologic Testing      1783




           A                                                                                                                    B




          FIGURE 128-5 A and B, Helical computed tomography scan
          postprocessed using the maximum intensity projection format in
          axial (A) and coronal (B) projections reveals significant left renal
          artery stenosis. C, The same scan postprocessed using surface-
          shaded display format.




                                                                                                                                C




constriction. Subsequent models were devised that clarified                      found to have anatomic evidence of RAS and improve the
further the pathophysiology of different patterns of renal                      success of revascularization. Despite the plethora of
artery obstruction. Stenosis of a single renal artery and                       physiologic studies that have been evaluated and used
consequent renal hypoperfusion leads to the release of renin                    clinically, the perfect test remains elusive. Studies that are
and an increase in the level of angiotensin. Angiotensin                        currently available are evaluated here.
produces direct vasoconstriction and sodium and fluid
retention. Patients with a normal functioning contralateral
kidney are able to correct for this volume expansion                            Renal Vein Renins
partially with a compensatory natriuresis.                                      Intravenous pyelography and plasma vein renin levels are
   A variety of noninvasive physiologic tests have been                         mentioned only for their historical significance. Neither
developed and evaluated. An accurate noninvasive physiologic                    intravenous pyelography nor plasma vein renin level is
test could serve as a screening test for RAS. A physiologic                     currently used, and neither was found to predict patients
test could prove functional significance in patients who are                     with RAS. Renal vein renins are still used as a method for
1784      Section XIX       THE MANAGEMENT OF RENOVASCULAR DISORDERS


detecting RAS in some centers. Catheterization of the renal       inhibitor renography cannot rule out RAS, however, in an
veins is an involved and invasive procedure, which is not         azotemia patient or in patients with bilateral disease. Both
appropriate for screening. Renal vein renins have been            subgroups are among the most important patients who
proposed as a method for determining which patients with          require treatment.
RAS would respond favorably to revascularization. Patients
with renin-induced renovascular hypertension have high
renin levels in the venous drainage of the affected kidney        ■        SUGGESTED PARADIGM FOR
and suppressed renin levels in the contralateral renal vein.               DIAGNOSIS OF SUSPECTED
Many investigators have found a correlation between
renal vein renins and a favorable response to surgery. The                 RENAL ARTERY DISEASE
usefulness of this test is limited, however, because absence      Renal artery disease is a complex disorder that can have
of a significant difference in renal vein renins does not          many causes and different clinical presentations. A rigid
always correlate with lack of benefit of revascularization. Of     diagnostic approach to suspected RAS is neither possible
patients with a negative test, 57% still have improvement         nor advisable. Instead, it is more prudent to adopt a flexible
after renal reconstruction.192-194 As might be anticipated,       strategy that is based on each patient’s clinical presentation
patients with bilateral RAS often fail to lateralize. Selective   and on “local expertise” with the various diagnostic modali-
sampling often misses accessory renal artery stenoses that        ties. General recommendations for the diagnostic approach
produce renin hypersecretion in only a segment of the             to patients thought to have RAS follow.
affected kidney, especially if there is separate venous               When there is strong clinical suspicion of renovascular
drainage for that segment. This test is still used occasionally   hypertension, and fibromuscular disease is the presumed
with the caveat that a positive study is meaningful, whereas      cause, it may be appropriate to proceed directly to contrast
a negative study should be placed in the context of the           angiography because of the relatively high incidence of
patient’s overall clinical presentation.                          distal and accessory renal artery lesions. No noninvasive
                                                                  imaging study currently available provides the necessary
                                                                  precision in detecting these lesions.
Radionuclide Renography                                               A traditional functional or physiologic diagnostic test can
A variety of radioisotopes can be used to determine renal         be used to verify the diagnosis and predict response to
blood flow and GFR. In addition, images obtained can               revascularization in patients who have normal renal
be used to estimate kidney size. Interest in using nuclear        function, who have suspected unilateral stenoses, and who
scintigraphy to diagnose RAS was renewed with the addi-           can tolerate temporary withdrawal of certain antihyper-
tion of angiotensin-converting enzyme (ACE) inhibitors            tensive medications. The number of patients thought to have
to the regimen. Protocols for the test vary among institu-        RAS who have impaired renal function or who cannot
tions. Typically, after similar preparation to that used for      discontinue hypertensive medications is increasing. These
non–ACE-enhanced scans, 25 to 50 mg of captopril is given         patients are not optimal candidates for physiologic testing,
after a baseline scan, and repeat images are obtained             and noninvasive renal artery imaging is advisable for them.
60 minutes later. In a kidney affected with RAS, the              Which noninvasive modality should be used is largely a
angiotensin II–induced vasoconstriction of the efferent           matter of local expertise. If there is a vascular laboratory
arteriole is acutely reduced, decreasing the GFR in that          with a dedicated technician who has documented profi-
kidney selectively; this is shown by a decrease in the relative   ciency with renal artery duplex ultrasonography, this would
GFR in the affected kidney compared with a baseline scan.         be the diagnostic modality of choice. Alternatively, if
The normal kidney responds with an increase in perfusion.         there is a radiologist with experience in three-dimensional
Criteria that suggest RAS are delayed time to maximal             gadolinium-enhanced MRA, MRA may be more appro-
uptake (>11 minutes) in the affected kidney, significant           priate. Experience with spiral CT is less extensive than with
asymmetry in uptake between kidneys, cortical retention of        the other two modalities, but further development of this
radionuclide with captopril, and marked reduction of GFR          technique is expected to make it a viable approach in
after captopril.195                                               selected patients with normal renal function. Although
   Initial reports of this technique were quite promising.        technologic advances will continue to improve the accuracy
Setaro and coauthors,196 in a study of 90 patients, showed a      of noninvasive imaging for suspected RAS, sound clinical
sensitivity of 91% and a specificity of 94% in the detec-          judgment is still paramount to the diagnosis and evaluation
tion of RAS greater than 50%. Several other investigators         of this complicated disorder.
have reported similar results.197,198 Although a significant
improvement over scintigraphy alone, captopril scanning is
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