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Chapter 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 less reliable in patients with signiﬁcant parenchymal disease ■ REFERENCES or bilateral stenoses. In a large European trial, the positive 1. Pickering TG: Diagnosis and evaluation of renovascular hypertension: predictive value of this test decreased from 88% to 57% in Indications for therapy. Circulation 83(Suppl I):I-147-I-154, 1991. patients with plasma creatinine greater than 1.5 mg/dL.199 2. 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