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Detection of Renal Artery Stenosis:

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  • 1. AJR:177, November 2001 1123 Detection of Renal Artery Stenosis: Prospective Comparison of Captopril-Enhanced Doppler Sonography, Captopril-Enhanced Scintigraphy, and MR Angiography OBJECTIVE. The objective of our study was to compare the value of captopril-enhanced Doppler sonography, captopril-enhanced renal scintigraphy, and gadolinium-enhanced MR angiography for detecting renal artery stenosis. SUBJECTS AND METHODS. Forty-one patients with suspected renovascular hyper- tension were prospectively examined with captopril-enhanced Doppler sonography, captopril- enhanced renal scintigraphy, gadolinium-enhanced MR angiography, and catheter angiography. The sensitivity and specificity of each technique for detecting renal artery stenosis measuring 50% or greater and 70% or greater were compared using the McNemar test. Positive and neg- ative predictive values were estimated for populations with 5% and 30% prevalence of renal artery stenosis. Kappa values for interobserver agreement were assessed for both gadolinium- enhanced MR angiography and catheter angiography. RESULTS. For detecting renal artery stenosis measuring 50% or greater, the sensitivity of gadolinium-enhanced MR angiography (96.6%) was greater than that of captopril-enhanced Doppler sonography (69%, p = 0.005) and captopril-enhanced renal scintigraphy (41.4%, p = 0.001). No significant difference in specificity was observed among modalities. For renal artery stenosis measuring 50% or greater, positive and negative predictive values were respectively 62% and 86% for captopril-enhanced Doppler sonography, 49% and 76% for captopril-enhanced renal scintigraphy, and 53% and 98% for gadolinium-enhanced MR angiography. Interob- server agreement was high for both gadolinium-enhanced MR angiography (κ = 0.829) and catheter angiography (κ = 0.729). CONCLUSION. Gadolinium-enhanced MR angiography is the most accurate noninvasive modality for detecting renal artery stenosis greater than or equal to 50%. The use of captopril-en- hanced Doppler sonography in combination with gadolinium-enhanced MR angiography for identifying renal artery stenosis needs to be evaluated with a cost-effectiveness analysis. enal artery stenosis is the leading cause of curable hypertension. Es- timates suggest that the prevalence of renovascular disease as a cause of hyperten- sion ranges from 0.5% to 5% in the general population [1, 2] to as high as 45% in selected patients with suggestive clinical features [3]. Catheter angiography, which is accepted as the gold standard for the detection of renal artery stenosis, is not an ideal screening method be- cause it is invasive and expensive. Catheter an- giography requires administration of iodinated contrast material and exposure to ionizing ra- diation. A reliable noninvasive diagnostic test is needed to select patients for invasive diag- nostic and therapeutic approaches. During the last decades, several noninvasive imaging modalities have been evaluated for their ability to detect renal artery stenosis. Renal scin- tigraphy [4–10] and Doppler sonography [11– 15] that show captopril-induced changes provide indirect evidence of the presence of renal artery stenosis and have proven helpful in screening patients with this condition. However, data con- cerning the reliability of these techniques are in- consistent and vary among studies. Many authors have reported disappointing results for both techniques [7, 16–22]. More recently, sub- stantial advances have been achieved with gadolinium-enhanced three-dimensional MR angiography for the identification of renal artery stenosis [23–27]. Yet the value of noninvasive modalities for the detection of renal artery steno- sis has not been sufficiently defined, and the most useful diagnostic strategy remains undeter- mined. Furthermore, the performance of a given Salah D. Qanadli1 Gilles Soulez1 Eric Therasse2 Viviane Nicolet1 Sophie Turpin3 Daniel Froment4 Maryse Courteau4 Marie-Claude Guertin5 Vincent L. Oliva1 Received August 9, 2000; accepted after revision April 26, 2001. Supported by operating grant MA15225 of the Medical Research Council of Canada. S. Qanadli was supported by a grant of the Société Française de Radiologie. 1 Department of Radiology, CHUM, Hôpital Notre-Dame, 1560 Sherbrooke St. E., Montréal, Quebec H2L 4M1, Canada. Address correspondence to G. Soulez. 2 Department of Radiology, CHUM, Hôpital Hotel-Dieu de Montréal, University of Montréal, 3840 St. Urbain, H2W 1T8 Montréal, Quebec, Canada. 3 Department of Nuclear Medicine, CHUM, Hôpital Hotel- Dieu de Montréal, University of Montréal, H2W 1T8 Montréal, Quebec, Canada. 4 Department of Medicine, CHUM, Hôpital Notre-Dame, Montréal, Quebec H2L 4M1, Canada. 5 Department of Biostatistics, Hotel-Dieu de Montréal, University of Montréal, Montréal, Quebec H2L 4M1, Canada. AJR 2001;177:1123–1129 0361–803X/01/1775–1123 © American Roentgen Ray Society R
  • 2. 1124 AJR:177, November 2001 Qanadli et al. screening modality can be influenced by the prevalence of true renovascular disease in the population studied. Thus, prospective compari- sons are needed to evaluate the value of each modality and to identify a clear diagnostic strat- egy. Our study was designed to compare the ac- curacy of captopril-enhanced renal scintigraphy, captopril-enhanced Doppler sonography and ga- dolinium-enhanced MR angiography for the de- tection of renal artery stenosis in patients with clinically suspected renovascular hypertension, and to determine the predictive value of these methods for identifying renal artery stenosis both in nonselected populations and in popula- tions selected on the basis of clinical features. Subjects and Methods Between January 1998 and May 1999, 41 pa- tients (15 men, 26 women; age range, 41–78 years; mean, 64 years) were prospectively enrolled in this study. Patient selection was based on the presence of one or several of the following clinical features: onset of hypertension before the age of 25 years or after 45 years; severe hypertension (malignant hypertension, grade III or IV retinopa- thy, hypertensive encephalopathy, or diastolic blood pressure > 115 mm Hg); refractory hyper- tension (systolic blood pressure > 160 mm Hg or diastolic blood pressure > 95 mm Hg despite opti- mal doses of three antihypertensive drugs); accel- eration of hypertension by more than 15% within the preceding 6 months; or abdominal or flank bruit. During this time, 30 patients were not in- cluded in the study for one or more of the follow- ing reasons: creatinine clearance of less than 40 mL/min; hyperkalemia (potassium > 5.5 mmol/L), because of the risk of nephrotoxicity induced by iodinated contrast material; history of stroke or transient ischemic attack with a carotid bruit, be- cause of the risk of hypotension induced by capto- pril; history of allergy to angiotensin-converting enzyme inhibitors or iodinated contrast material; or contraindications to MR imaging (e.g., pace- maker, ocular metallic foreign bodies). Thirty-six additional patients refused to undergo all examina- tions, sometimes because they had undergone one or more noninvasive studies with a normal result. The mean arterial systolic over diastolic blood pressure of the study population was 162 ± 23 over 85 ± 12 mm Hg and the mean creatinine clearance level was 107 ± 38 mL/min. Forty of the study patients had two kidneys and one had a soli- tary kidney, for a total of 81 kidneys studied. All patients underwent intrarenal Doppler sonography before and after captopril administra- tion, captopril-enhanced scintigraphy, gadolinium- enhanced MR angiography, and catheter angiography within a 3-month period. The sequence of exami- nations depended on the accessibility of the imag- ing modality at the time of imaging. Angiotensin- converting enzyme inhibitors and calcium block- ers were discontinued 2–5 days (depending on the half-life of the medication) before radionuclide and Doppler sonographic examinations [10]. No surgery or endovascular procedure was done be- tween any imaging modalities. The study was approved by our institutional ethics and research committees, and written in- formed consent was obtained from all patients. Doppler Sonography Doppler sonographic examinations were per- formed with a Spectra unit (Diasonics, Milpitas, CA) equipped with a 3.5-MHz phased array trans- ducer. After we identified intrarenal arteries with color-flow imaging using a posterior oblique ap- proach, spectral velocity waveforms were obtained at an angle of insonation of less than 60° from seg- mental arteries at the superior, mid (anterior and posterior), and inferior portions of the kidney. We used the smallest velocity scale, the lowest wall filter, and a sweep time of 2 sec. Each patient un- derwent two Doppler sonographic examinations using the same technique: the first, baseline exam- ination was followed by a second examination per- formed 1 hr after the oral administration of 25 mg of captopril, in keeping with the recommendations of the consensus report on angiotensin-converting enzyme inhibitors for detecting renovascular hy- pertension [10]. We used a pattern recognition ap- proach according to previously published criteria [15]. The most abnormal Doppler spectrum (pro- vided that it was reproducible) was selected by the investigator for each kidney before and after the administration of captopril and was morphologi- cally classified into one of the three types de- scribed by Oliva et al. [15]. Type A represents a normal spectrum with an early systolic peak and a steep linear early systolic rise. Type B includes a normal spectrum without an early systolic peak but with a steep linear early systolic rise. Type C represents abnormal spectrum with a decrease of the early systolic rise. A type C Doppler spectrum was considered indicative of renal artery stenosis. Additional measurements of the resistive index, acceleration, and acceleration time of early sys- tolic rise were obtained for the selected Doppler spectrum. Acceleration and acceleration time thresholds for positive results were set at 390 cm/ sec2 and 0.06 sec, respectively, for the baseline ex- amination and at 440 cm/sec2 and 0.09 sec for the captopril-enhanced examination [15]. For each kidney, Doppler findings were considered positive if either the quantitative (acceleration, time of ac- celeration) or morphologic (pattern recognition) evaluation was abnormal. In cases of disagreement between quantitative and qualitative (pattern rec- ognition) evaluations, assessment of renal artery patency was based on pattern recognition, given the high interobserver correlation previously es- tablished with this method (κ = 0.95) [15]. Direct Doppler imaging of the proximal renal arteries could not be performed consistently because of technical limitations. Therefore, only intrarenal Doppler sonography was used for this comparative study in order to minimize the number of exclu- sions. The investigator’s level of confidence in the captopril-enhanced Doppler sonography interpre- tation was rated on a five-point scale as follows: very high, high, fair, low, and very low. All examinations were performed and analyzed by one of two investigators who were unaware of the findings of the other techniques. Scintigraphy Baseline and captopril-enhanced 99mTc-mercap- toacetyltriglycine (99mTc-MAG3) scintigraphy was performed in all patients using a 1-day, 25-mg capto- pril protocol as recommended by the Working Party Group on Determining the Radionuclide of Choice [28]. 99mTc-MAG3 is a protein-bound radiopharma- ceutical tracer, and its clearance is almost exclusively through tubular secretion. 99mTc-MAG3 was pre- ferred to other tracers because of the high extraction efficiencies, its image quality, and its favorable dosim- etry. Patients were instructed to be well hydrated be- fore the examination. Because chronic administration of angiotensin-converting enzyme inhibitors may re- duce the sensitivity of scintigraphy, this medication was withheld from all patients for 2–5 days before the examination and was replaced by other drugs when indicated. A large-field-of-view gamma camera inter- faced with a computer was positioned beneath the pa- tient to obtain standard posterior views of the kidneys. Images were stored in a 64 × 64 word-mode pixel ma- trix. Time–activity curves were generated. Data were obtained for a minimum of 30 min. After the baseline study, an oral dose of 25 mg of captopril was adminis- tered, and the patient was instructed to drink 300–500 mL of water. The patient was then placed in the su- pine position and blood pressure was monitored at frequent intervals. The captopril-enhanced study was initiated 60 min after captopril administration. Results were interpreted according to the guidelines of the So- ciety of Nuclear Medicine [29]. The most important criterion for detecting renal artery stenosis was unilat- eral parenchymal retention of the radiopharmaceutical after captopril administration.A change in the 20-min to maximum uptake ratio of 0.15 or greater, an in- creased delay of 2 min before maximum uptake, or changes superior or equal to 2 in the renogram grade (from a 5-level scale) were considered indicative of renal artery stenosis. Patients with abnormal baseline findings indicative of reduced renal function that were not modified after captopril administration were con- sidered to have an intermediate probability of renal ar- tery stenosis. All examinations were performed and inter- preted by one investigator who was unaware of the findings of the other imaging studies. MR Angiography MR angiography was performed with 1.5-T unit (Magnetom Vision; Siemens, Erlangen, Ger- many) using a phased array body coil. Examina- tion of renal arteries consisted of two sequences in the coronal plane: before and during a dynamic IV administration of 0.2 mmol/kg of body weight of gadopentetate dimeglumine (Magnevist; Berlex Canada, Montreal, Canada) to provide background
  • 3. Sonography, Scintigraphy, and MR Angiography of Renal Artery Stenosis AJR:177, November 2001 1125 subtraction and to increase vessel-to-background contrast. Images were acquired with the following parameters in a single breath-hold: three-dimen- sional gradient-echo technique; TR/TE, 3.4/1.4 msec; receiver bandwidth, 890 Hz per pixel; field of view, 300 × 300 mm2; matrix, 128 × 256; vol- ume coverage, 100 mm; slice thickness, 1.8 mm (after interpolation, the effective thickness was 0.9 mm); scanning time, 25 sec. The contrast material was administered at a rate of 1.5–2 mL/sec. The transit time of the contrast material was deter- mined using a test-bolus sequence of 2 mL and dy- namic region-of-interest analysis of the signal intensity at the level of the renal arteries. Image acquisition was started 2 sec before the signal in- tensity peak. In all patients, T1- and T2-weighted fast spin-echo sequences were obtained before gadolinium-enhanced MR angiography to evaluate the morphologic status of the kidneys, such as the parenchymal volume and signal. Maximum-inten- sity-projection reconstructions and multiplanar reformations were processed after subtraction. Gadolinium-enhanced MR angiography exami- nations were reviewed by two independent investi- gators without knowledge of the results of any other examination. Renal angiograms were graded for im- age quality using a three-point scale: optimal, when a high degree of contrast enhancement was obtained without motion artifacts; suboptimal, when the quality was sufficient for analysis of the main renal arteries but without a high degree of contrast en- hancement; and inconclusive, when poor opacifica- tion or major motion artifacts were observed. Combined analysis of source images, maximum- intensity-projection reconstructions, and multipla- nar reformations was used to analyze renal arteries and to quantify stenosis. The percentage of stenosis was calculated using a precision caliper, a magnify- ing lens, and the following formula: (D – d) / D × 100, where D is the diameter of the uninvolved seg- ment of renal artery and d is the diameter of the stenotic segment. In cases of multiple renal arteries, the most stenotic artery was considered. When more than one stenosis were identified in a single renal ar- tery, the most severe stenosis was used for analysis. In cases of intravascular signal void, renal artery stenosis was considered greater than 70%. Catheter Angiography Catheter angiography was performed on a digi- tal subtraction system (DFP 2000; Toshiba Medi- cal System, Otawara-Shi, Japan) through the femoral approach in all patients using a 5-French pigtail catheter introduced with the Seldinger tech- nique. A standard posteroanterior projection of the abdominal aorta was obtained in all patients using 40 mL of 32% iodinated contrast material (Visi- paque 320; Nycomed Imaging, Ontario, Canada) injected at a rate of 20 mL/sec. Additional projec- tions and selective angiograms were obtained if necessary at the discretion of the investigator. All angiograms were reviewed independently by the same two investigators who reviewed gado- linium-enhanced MR angiographic examinations. A minimum delay of 1 month was observed be- tween gadolinium-enhanced MR angiography and catheter angiography interpretation sessions. The identification of patients was concealed to avoid bias resulting from patient recognition. The cathe- ter angiography interpretation session was done after the gadolinium-enhanced MR angiography interpretation session. Investigators analyzed im- age quality and measured renal artery stenosis in the same manner as for gadolinium-enhanced MR angiography. To categorize kidneys and patients with catheter angiography, two thresholds—50% and 70%—were used to define renal artery steno- sis. Discrepancies among investigators that led to the classification of renal artery stenosis into dif- ferent categories at catheter angiography were re- solved by consensual interpretation to establish the standard of reference. Data Analysis Kidneys in which at least one examination was inconclusive were excluded from the comparative analysis. According to the findings in each modal- ity, kidneys and patients were classified using a two-point scale as follows: absence of renal artery stenosis, or presence of renal artery stenosis. Cath- eter angiography was considered the standard of reference. Indeterminate results with captopril-en- hanced Doppler sonography or captopril-enhanced scintigraphy were considered positive to facilitate statistical analysis. This attitude is also in keeping with our usual clinical practice. The sensitivity and specificity for renal artery stenosis detection were calculated for each tech- nique on the basis of the findings at catheter an- giography using 50% and 70% thresholds for renal artery stenosis. The McNemar test was used to compare the obtained values. For gadolinium-en- hanced MR angiography, the results of the first in- vestigator were used for the comparative analysis. The predictive value of each technique for de- tecting renal artery stenosis greater than or equal to 50% was estimated using Bayesian analysis for a nonselected population (with a 5% renal artery stenosis prevalence [30]) and for a population se- lected on the basis of clinical criteria (the preva- lence of renal artery stenosis was set at 30% according to previously published data [1]). The interobserver variability for interpreting gad- olinium-enhanced MR angiography and catheter an- giography was assessed using the kappa value and intraclass correlation coefficient. On the basis of the kappa value, agreement was defined as follows: poor, less than 0.20; fair, 0.21–0.40; moderate, 0.41– 0.60; good, 0.61–0.800; and excellent, 0.80–1.00. A 95% confidence interval (CI) was assigned to the calculated kappa value. The degrees of stenosis mea- sured with gadolinium-enhanced MR angiography and with catheter angiography were compared in kidneys with renal artery stenosis greater than or equal to 50% using the Student’s t test. Statistical analysis was performed with a statis- tical software system (SAS for Windows, version 6.12; SAS Institute, Cary, NC). Differences were considered statistically significant when p values were less than 0.05. Results Catheter angiography was considered opti- mal in 98% (investigator 1, 99%; investigator 2, 97%) of kidneys and suboptimal in 2% (in- vestigator 1, 1%; investigator 2, 3%). Ninety renal arteries, including nine accessory or mul- tiple arteries, were identified in the 81 kidneys. Intrarenal artery Doppler waveforms were ob- tained in all kidneys studied. Doppler exami- nations were scored with a high or very high level of confidence in 66 kidneys (81%). Only two examinations (2%) had a low or very low level of confidence. Captopril-enhanced renal scintigraphic examinations were available and were considered diagnostic in all kidneys. Gadolinium-enhanced MR angiography ex- aminations were considered optimal in 72% of kidneys (investigator 1, 75%; investigator 2, 69%) and suboptimal in 25% (investigator 1, 22%; investigator 2, 28%). In one patient, both the left and the right gadolinium-enhanced MR angiography renal angiograms (2%) were considered inconclusive and were excluded from statistical analysis. Therefore, 79 kidneys were available for the comparative study. All but three accessory renal arteries identified at catheter angiography were visualized on gado- linium-enhanced MR angiography. Catheter angiography revealed the pres- ence of renal artery stenosis greater than or equal to 50% in 31 (76%) of 41 patients and in 41 (52%) of 79 kidneys. The population with renal artery stenosis (mean degree of stenosis, 68 ± 11%) consisted of 12 men and 19 women having a mean age of 65 ± 9 years and a mean arterial systolic over diastolic blood pressure of 163 ± 22 over 84 ± 12 mm Hg. Twenty-seven patients had atheroscle- rotic lesions, and four patients had fibromus- cular dysplasia. Three kidneys had a totally occluded renal artery. The nonstenotic popu- lation (mean degree of stenosis, 20 ± 19) consisted of three men and seven women having a mean age of 60 ± 11 years and a mean arterial systolic over diastolic blood pressure of 160 ± 27 over 87 ± 17 mm Hg. The mean standard deviation between the two investigators for the degree of stenosis determined with catheter angiography was 9% (range, 0–41%). Concordance between investigators in quantifying the degree of stenosis was excellent, with an intraclass correlation coefficient of 0.90. When kidneys were categorized using the two-point ordinal scale with a 50% threshold, disagreement oc-
  • 4. 1126 AJR:177, November 2001 Qanadli et al. curred in 11 kidneys, with a kappa value of 0.729 (range, 0.581–0.877). When the threshold was set at 70%, agreement re- mained good despite a slight decrease of the kappa value to 0.691 (range, 0.495–0.887). Agreement between investigators for renal artery stenosis quantification with gadolin- ium-enhanced MR angiography (intraclass correlation coefficient = 0.88) was similar to that observed with catheter angiography (in- traclass correlation coefficient = 0.90). The mean standard deviation between the two in- terpreters of gadolinium-enhanced MR an- giography for the degree of stenosis was 10% (range, 0–74%). Agreement between investigators measured with kappa coeffi- cients calculated with 95% CIs for identify- ing renal artery stenosis measuring 50% or greater was excellent for gadolinium-en- hanced MR angiography (κ = 0.829 [95% CI, 0.699–0.959]) and good for catheter an- giography (κ = 0.0.729 [95% CI, 0.581– 0.877]). However, kappa values were slightly lower for the 70% threshold than for the 50% threshold. With the 70% threshold, kappa values were considered good (κ = 0.691 [95% CI, 0.495–0.887]) for catheter angiog- raphy and moderate (κ = 0.592 [95% CI, 0.385–0.799]) for gadolinium-enhanced MR angiography. Compared with catheter an- giography, gadolinium-enhanced MR an- giography overestimated the degree of stenosis (Fig. 1). Among 41 kidneys with re- nal artery stenosis greater than or equal to 50%, the degree of stenosis observed was 78% ± 22% for gadolinium-enhanced MR angiography as compared with 69% ± 14% for catheter angiography (p = 0.003). Sensitivity and specificity for detecting re- nal artery stenosis with thresholds of 50% and 70% are reported in Table 1. The sensitivity of gadolinium-enhanced MR angiography was C BA Fig. 1.—76-year-old man with severe hypertension. Radiologic investigation revealed discrepancy be- tween MR angiography and catheter angiography. A, Catheter angiogram reveals bilateral renal artery stenosis. Right renal artery stenosis (arrow) was consid- ered meaningful using 50% threshold and insignificant using 70% threshold (measurement of investigator 1: 54%; investigator 2: 64%). Similarly, left renal artery stenosis (arrowhead) was meaningful for 50% threshold and insignificant for 70% threshold (investigator 1: 58%; investigator 2: 54%). B, Maximum-intensity-projection reconstruction obtained from gadolinium-enhanced MR angiography shows bilat- eral renal artery stenoses. However, degree of stenosis was overestimated as compared with catheter angiogra- phy. Right renal artery stenosis (long arrow) was consid- ered meaningful using 70% threshold by second investigator (investigator 1, 63%; investigator 2: 71%) and left renal artery stenosis (short arrow) was considered meaningful using70%thresholdbyfirstinvestigator(investi- gator 1: 75%; investigator 2: 61%), thus resulting in false- positiveresultsforgadolinium-enhancedMRangiography. C, Intrarenal Doppler waveform obtained from right kid- ney 1 hr after captopril administration. Systolic rise is perfectly straight (arrow), indicating a normal finding. Left renal Doppler study had equally normal findings.
  • 5. Sonography, Scintigraphy, and MR Angiography of Renal Artery Stenosis AJR:177, November 2001 1127 significantly higher than that of captopril-en- hanced renal scintigraphy for both the 50% and 70% thresholds both in the kidney and in the patient populations (Tables 2 and 3). The sensitivity of gadolinium-enhanced MR an- giography was superior to that of captopril-en- hanced Doppler sonography, but the difference reached statistical significance only for the 50% renal artery stenosis threshold. The sensi- tivity of captopril-enhanced Doppler sonogra- phy was significantly greater than that of captopril-enhanced scintigraphy for both 50% and 70% thresholds for renal artery stenosis. No significant difference of the specificity was ob- served among the modalities, except for gad- olinium-enhanced MR angiography (79.5%) and captopril-enhanced Doppler sonography (94.9%), for a 50% threshold for renal artery stenosis in the kidney population (p = 0.03). Because of a high prevalence of renal artery stenosis in our study population, positive and negative predictive values were estimated using Bayesian analysis for a 30% renal artery steno- sis prevalence, as reported in highly selected populations [1]. For detecting renal artery steno- sis greater than 50%, positive and negative pre- dictive values were respectively 62% and 86% for captopril-enhanced Doppler sonography, 49% and 76% for captopril-enhanced scintigra- phy, and 53% and 98% for gadolinium-en- hanced MR angiography. In a nonselected population with a 5% prevalence of renal artery stenosis, positive predictive values were 16%, 10%, and 14% for captopril-enhanced Doppler sonography, captopril-enhanced scintigraphy, and gadolinium-enhanced MR angiography, re- spectively; and negative predictive values were 98%, 96%, and 100%, respectively. Three patients had stenosis greater than 50% caused by fibromuscular dysplasia. In this group of patients, renal artery stenosis was accurately diagnosed using scintigraphy in one patient, using Doppler sonography in one patient, and using MR angiography in two patients. Discussion Despite the importance of identifying ren- ovascular disease, a reliable noninvasive tech- nique to detect renal artery stenosis in patients with hypertension has not been clearly estab- lished. A reliable noninvasive technique is of paramount importance to select patients with suspected renal artery stenosis for subsequent revascularization procedures and also to avoid unnecessary catheter angiography in patients without substantial renal artery stenosis. Incon- sistencies are apparent in the literature regarding noninvasive techniques, especially sonography [16, 17, 19, 31] and radionuclide studies [7, 20, 22]. Consequently, we designed our study to prospectively compare the three leading nonin- vasive techniques. Most studies define renal ar- tery stenosis as a reduction in diameter greater than 50% based on morphologic evaluation of the renal artery [32]. However, some authors ar- gue that only stenoses greater than 70% should be considered hemodynamically significant [32–34]. For this reason, we evaluated the accu- racy of each technique using two renal artery stenosis thresholds, 50% and 70%. Our results show that gadolinium-enhanced MR angiography has a high sensitivity for de- tection of renal artery stenosis and is probably Note.—CDS = captopril-enhanced Doppler sonography, CRS = captopril-enhanced renal scintigraphy, MRA = gadolinium-enhanced MR angiography. TABLE 1 Sensitivity and Specificity of Noninvasive Techniques Calculated for 50% and 70% Thresholds for Renal Artery Stenosis Variable Analysis by Kidney Analysis by Patient Stenosis ≥ 50% Stenosis ≥ 70% Stenosis ≥ 50% Stenosis ≥ 70% CDS CRS MRA CDS CRS MRA CDS CRS MRA CDS CRS MRA Sensitivity Percent 62.5 32.5 90.0 79.0 47.4 94.7 69.0 41.4 96.6 87.5 56.3 93.8 Number 25/40 13/40 36/40 15/19 9/19 18/19 20/29 12/29 28/29 14/16 9/16 15/16 Specificity Percent 94.9 92.3 79.5 80.0 88.3 81.7 81.8 81.8 63.6 66.7 79.2 62.5 Number 37/39 36/39 31/39 48/60 53/60 49/60 9/11 9/11 7/11 16/24 19/24 15/24 Note.—Data are p values, which were considered significant at less than 0.05 (McNemar test). CDS = captopril-enhanced Doppler sonography, CRS = captopril-enhanced renal scintigraphy, MRA = gadolinium-enhanced MR angiography. Dash (—) indicates not applicable. TABLE 2 Comparison of Sensitivity and Specificity of Noninvasive Techniques for Detection of Renal Artery Stenosis in 79 Kidneys Imaging Type Stenosis ≥ 50% Stenosis ≥ 70% Sensitivity Specificity Sensitivity Specificity CDS CRS CDS CRS CDS CRS CDS CRS CRS 0.001 — 0.564 — 0.034 — 0.096 — MRA 0.001 0.001 0.034 0.132 0.180 0.003 0.763 0.206 Note.—Data are p values, which were considered significant at less than 0.05 (McNemar test). CDS = captopril-enhanced Doppler sonography, CRS = captopril-enhanced renal scintigraphy, MRA = gadolinium-enhanced MR angiography. Dash (—) indicates not applicable. TABLE 3 Comparison of Sensitivity and Specificity of Noninvasive Techniques for Detection of Renal Artery Stenosis in 40 Patients Imaging Type Stenosis ≥ 50% Stenosis ≥ 70% Sensitivity Specificity Sensitivity Specificity CDS CRS CDS CRS CDS CRS CDS CRS CRS 0.005 — 1.000 — 0.025 — 0.180 — MRA 0.005 0.001 0.317 0.414 0.564 0.014 0.739 0.157
  • 6. 1128 AJR:177, November 2001 Qanadli et al. the most useful noninvasive tool in a high-prev- alence population. We observed that normal re- sults on gadolinium-enhanced MR angiography could convincingly exclude renal artery stenosis in 98% of cases. However, gadolinium-en- hanced MR angiography has a low positive pre- dictive value (53%) even in a selected population. This low value could be explained by overestimation of the degree of stenosis with gadolinium-enhanced MR angiography as com- pared with catheter angiography. In fact, the positive predictive value of captopril-enhanced Doppler sonography was greater (62%) than that of gadolinium-enhanced MR angiography. However, we could not reproduce the diagnos- tic performance of intrarenal captopril-en- hanced Doppler sonography reported in earlier studies [13, 15]; this discrepancy may be related to their design, which consisted of a retrospec- tive review of patients who underwent capto- pril-enhanced Doppler sonography and catheter angiography, without systematic validation with catheter angiography of negative Doppler sonography results. The sensitivity of captopril- enhanced Doppler sonography in our study (analysis by patients) was fair (69%) for detect- ing renal artery stenosis measuring 50% or greater and good (87.5%) for detecting 70% re- nal artery stenosis. One limitation of our study is the absence of evaluation of the main renal ar- tery with color Doppler sonography. The accu- racy of captopril-enhanced Doppler sonography could be increased by systematically analyzing proximal renal arteries using a direct approach, but this technique is limited by technical failure in 25– 42% of cases [16, 17, 35]. Furthermore, this technique is often inadequate for identify- ing accessory renal arteries, which are present in approximately 20% of patients [16, 17]. On a positive note, there is hope that the use of sono- graphic contrast agents will improve the evalua- tion of proximal renal arteries [36, 37]. We observed a poor accuracy for captopril- enhanced scintigraphy for detecting moderate and severe renal artery stenosis, with significantly lower sensitivity than that of gadolinium-en- hanced MR angiography and captopril-enhanced Doppler sonography. Our results suggest that captopril-enhanced scintigraphy may not be a useful screening test for renal artery stenosis in populations comparable to ours. In the litera- ture, the diagnostic performance of scintigraphy is much higher than that we report, with results of 51–96% [8]. We have no clear explanation for the poor performance of scintigraphy in our study. All patients had unenhanced and capto- pril-enhanced examinations performed after the discontinuance of angiotensin-converting en- zyme inhibitors, and only 10 patients (25%) had bilateral stenoses. The investigators who per- formed these examinations are specialists in renal scintigraphy. A possible explanation for our dis- crepant findings is that most of the results re- ported in the literature are based on retrospective studies.Those results can be influenced by a veri- fication bias often found in retrospective studies (only patients with positive findings undergo a confirmatory examination). Consequently, the proportion of false-negative examinations may not be evaluated properly, which could lead to an overestimated sensitivity. In our study, the perfor- mance of scintigraphy was evaluated prospec- tively and appears disappointing. A criticism of our study is the 75% prevalence of renal artery stenosis in our patient population. The admitted prevalence of renal artery stenosis after clinical selection of hypertensive patients is 30% [1, 38]. Therefore, our study population may not be representative of the target popula- tion, who should meet the selection criteria that we used. The prevalence of renal artery stenosis among all patients referred to our institution with clinically suspected renal artery stenosis during the study period was 41%. However, some clini- ciansandpatientswerereluctanttopursuefurther examinations in the study protocol after normal findings on Doppler sonography or scintigraphy. In fact, 36 patients in that situation refused to un- dergo angiography, which explains in large part why the prevalence of renal artery stenosis was further increased in our study population. An- other point of debate is that patients examined for renal artery stenosis in our study were selected on suggestive clinical features, which differs from the nonselected population of hypertensive pa- tients, of whom only 2–5% have renovascular disease [30, 38]. Considering this prevalence dif- ference we estimated the predictive values of each screening test in reference to a prevalence as great as 30% (clinically selected patients) and as low as 5% (nonselected patients). Given the lower availability and higher cost of gadolinium-enhanced MR angiography as compared with captopril-enhanced Doppler sonography, the relative place of these two screening tests remains to be determined. Con- sidering the low positive predictive value of gadolinium-enhanced MR angiography for identifying renal artery stenosis in nonselected patients, the use of this method should be re- served for selected patients. 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