Colour Doppler sonography to screen for renal artery stenosistechnical

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1 2385 Colour Doppler sonography to screen for renal artery stenosistechnical points to consider B. Krumme and L. C. Rump University Hospital Freiburg, Department of Internal Medicine, Freiburg, Germany Introduction The diagnosis of renal artery stenosis has been a challenge to the nephrologist and radiologist for decades. Selective renal arteriography is clearly the gold standard to visualize renal artery stenosis. Recently an alternative non-invasive diagnostic modality, i.e. colour Doppler sonography, has been developed to detect renal artery stenosis in hypertensive patients. Nevertheless colour Doppler screening of renal artery stenosis is not as simple as initially thought, and substantial controversy persists concerning the diagnostic value of this tool [1-7]. Operator dependency, technically inadequate visualization of main and accessory renal arteries, as well as uncertainties of intrarenal measurements have been the main points of discussion. Our comment focuses on technical aspects of colour Doppler sonography to optimize the use of this new non-invasive screening method for renal artery stenosis. The important issue of patient selection will not be dealt with. Technical equipment and examination procedure Two features facilitate the evaluation of blood flow velocities of the intra- and extrarenal arteries, i.e. the colour mode, based on pulsed wave (pw) Doppler technique and the use of lower frequency transducers (2.5-4 MHz) with better penetration to greater depths. However, very high velocities (>3m/s), which are often seen in patients with renal artery stenosis, cannot be correctly measured by pw-doppler because of the limits imposed by pulse repetition frequency. Therefore a colour Doppler unit should be equipped with pw- and cw-doppler, such as is usually available in echocardiography machines. The recently developed colour Doppler energy (CDE) technique, based on the integrated Doppler power spectrum, does not improve the results of blood flow velocity measurements in the extrarenal arteries. However, low flow signals of the interlobar and interlobular arteries can be easily detected by CDE [8]. Therefore this technique may be advantageous for the diagnosis of partial renal infarction, but angiograph- Correspondence and offprint requests to: Bernd Krumme MD, University Hospital Freiburg, Department of Internal Medicine, Hugstetter Str. 55, D Freiburg, Germany. ically controlled studies testing this hypothesis are not yet available. Patients should fast overnight to reduce bowel gas, which limits the visualization of the deeply located renal arteries. We start the investigation in supine position to visualize the origin and course of the renal arteries and to measure blood flow velocities in these vessels (Figure 1). Then, in right and left sided lateral decubitus position the renal parenchyma and the kidney size is documented by B-mode ultrasound. Furthermore, we recommend to measure intrarenal Doppler indices and extrarenal blood flow velocities in decubitus position as well. Because of lower Doppler angles, blood flow velocity is more accurately determined in decubitus than in supine position (Figure 2). Accessory renal arteries are detected more frequently by scanning the patients in decubitus position (Figure 3); however, only about 25% of all angiographically proven accessory renal arteries can be visualized [9]. If renal Doppler examination includes scanning of intra- and extrarenal arteries, it will take an average of 30 min, not taking into account the time required for documentation [9]. Doppler parameters of extrarenal arteries Stenoses can be identified with Doppler technique by the measurement of high blood flow velocities. Peak systolic and end-diastolic velocities were originally developed as parameters for stenoses of the carotid arteries and are useful for the detection of renal artery stenoses as well. Using peak systolic velocity ( cm/s) as criterion for the presence of renal artery stenosis sensitivities of 88-98% and specificities of 62-98% have been reported [4,6,10]. A recent study by Olin et al. [4] showed that 81% of the renal arteries had severe stenosis (>80%), when measured enddiastolic velocity exceeded 150 cm/s. Using the ratio of renal to aortic peak systolic velocity (renal aortic ratio >3.5) Hoffmann et al. [11] found an impressive sensitivity of 92%, but specificity was rather low, i.e. 62%. It is unwise to attribute too much significance to such sensitivity and specificity estimates, since the method is highly operator dependent. It is unwise to rely exclusively on extrarenal parameters for the screening of renal artery stenosis: 1. In several studies 10-42% of extrarenal arteries were not adequately visualized [1,2,11]. It goes without saying that the quality of Doppler examina-

2 2386 HRO I BUR G E H.HEX. Fig. 2. In patient's left-sided decubitus position the origin of a right renal artery (yellow colour) close to the abdominal aorta (red colour) is visualized from the right lateral side of the patient. Normal blood flow velocity of 142 cm/s is measured with an optimal Doppler beam angle of 0. tion largely depends on the experience and the dedication of the investigator who is willing to invest sufficient time for investigation. If the patient is scanned in multiple positions, as described above, 80% of all angiographically confirmed renal arteries can be visualized to measure blood flow velocities [9]. In most studies calculation of sensitivity and specificity was based on the number of renal arteries, visualized by colour Doppler sonography. This Fig. 1. The origin of the right renal artery (blue colour) is scanned in supine position and normal blood flow velocity (97 cm/s) is measured with a Doppler beam angle of 54.

3 2387 does not take account of arteries which have been missed by colour Doppler sonography but visualized by arteriography. As a consequence most of the reported rather high sensitivities are overestimated, so that comparisons to other screening methods, e.g. captopril scintigraphy, are inappropriate [12]. 3. It is possible to differentiate between normal and stenotic renal arteries by the evaluation of peak systolic and end-diastolic velocities. It is rather difficult, however, to determine the grading of renal artery stenoses by these parameters [4,9]. Recently a new intravenous contrast agent, consisting of microbubbles stabilized in a galactose matrix (Levovist, Schering), has been introduced for renal colour Doppler sonography [13]. One has to wait for the results of ongoing prospective multicentre trials to decide whether better results can be obtained by using contrast enhancement for visualization of the extrarenal arteries. Doppler parameters of intrarenal arteries As described above there are many problems in visualizing and examining the extrarenal arteries. Therefore the use of intrarenal blood flow as an index of renal artery stenosis has been evaluated [7,9,14-16]. Flow signals within the kidneys are easy to detect and in most cases they are not interfered with by obesity or excessive bowel gas. There are two possibilities to assess the intrarenal Doppler spectrum. One possibility is Doppler waveform analysis based on the phenomenon of the poststenotic tardus-parvus flow pattern. This analysis includes the calculation of systolic acceleration (m/s2), acceleration time (s), systolic deceleration (m/s2), systolic deceleration time (s), and last but not least the evaluation of an early systolic peak, that is missing in severe renal artery stenosis. However, the results of studies that investigated these parameters for the diagnosis of renal artery stenosis were not consistent [7,14,17]. In the majority of moderate renal artery stenoses no abnormality of Doppler waveform is noted [14]. Therefore we advise against relying exclusively on Doppler waveform analysis of intrarenal arteries for the colour Doppler sonography screening of renal artery stenosis. Another attractive alternative of intrarenal Doppler screening for renal artery stenosis is the calculation and side-to-side comparison of the resistive index (RI) and pulsatility index (PI), derived from the Doppler spectrum of the segmental and interlobar arteries [9,15,16]. If severe renal artery stenosis is present both intrarenal RI and PI of the poststenotic kidney decrease. A significant difference between the stenotic and the contralateral nonstenotic kidney is noted (Figure 4). A difference between the two kidneys is no longer reliable if bilateral renal artery stenosis is present. Furthermore, accuracy of the Doppler indices is limited in atherosclerotic renal artery stenosis, most probably due to the reduced elasticity of the renal arteries. For these reasons we caution against relying exclusively on these parameters for the diagnosis of renal artery stenosis. Using the side-to-side comparison of RI (ARI>0.05) as the only criterion for renal artery stenosis, we found a sensitivity of 64% and a specificity of 82% in 135 angiographically controlled patients [9]. Fig. 3. In left-sided decubitus position three right (red colour) renal arteries and one left renal artery (blue colour) are visualized by CDS.

4 /9 3 NEPHROLOGIE FREIBURG 01-MAR : V319 LE.KIDNEV MI N= 0.1: RI= 6. 5: L C A L I P E 10: AI V 31 9 R ES 1 7 r(i ft NEPHROLOGIE FREIBURG RI.KIDNEY M AX= IM I N = 0.1 RI= 0.4k L CALIPEF STENOTIC 0=0! (b) Fig. 4. (a) Normal intrarenal blood flow of a left kidney is measured (resistive index: 0.58) in a patient with a right sided severe renal artery stenosis, (b) In the same patient the poststenotic intrarenal flow pattern of the right kidney is obtained, indicating a significantly lower resistive index (resistive index: 0.40). The side-to-side-difference of the resistive index (0.18) is an intrarenal criterion of severe RAS. How can one overcome the limitations? If the two methods are not foolproof when used in isolation, what result can be obtained by combining the two [1,2,14]? In the above-mentioned prospective, angiographically controlled study we assessed simultaneously intrarenal ARI (ARI>0.05) and extrarenal peak systolic velocity (>2 m's). The combined assessment of both parameters increased sensitivity to 89% and specificity to 92% against angiography as the gold standard [9]. The latter point is important because it takes into account renal arteries which may have been missed by colour Doppler sonography. Consequently, for Doppler screening of renal artery stenosis we recommend the simultaneous assessment of both intra- and extrarenal parameters. This takes between 20 and 60 min, even less than required for other non-invasive screening methods as captopril scin- (a)

5 tigraphy or captopril test. Most probably in the near future the use of contrast enhancement will further speed up and improve the results of colour Doppler sonography screening for renal artery stenosis. Acknowledgements. We greatly thank the ACUSON Corporation, Mountain View, CA, USA for supporting the colour print reproduction. References 1. Desberg AL, Paushter DM, Lammert GK et al. Renal artery stenosis: evaluation with color Doppler flow imaging. Radiology 1990; 177: Berland LL, Koslin DB, Routh WD, Keller FS. Renal artery stenosis: prospective evaluation of diagnosis with color duplex US compared with angiography. Radiology 1990; 174: Bude RO, Rubin JM. Detection of renal artery stenosis with Doppler sonography: It is more complicated than originally thought. Radiology 1995; 196: Olin JW, Piedmonte MR, Young JR, DeAnna S, Grubb M, Childs MB. The utility of Duplex ultrasound scanning of the renal arteries for diagnosing significant renal artery stenosis. Ann Intern Med 1995; 122: Garel L, Dubois J, Robitaille P et al. Renovascular hypertension in children: Curability predicted with negative intrarenal Doppler US results. Radiology 1995; 195: Strandness E. Duplex imaging for the detection of renal artery stenosis. Am J Kidney Dis 1994; 24: Halpern EJ, Needleman L, Nack TL, East SA. Renal artery 2389 stenosis: should we study the main renal artery or segmental vessels? Radiology 1995; 195: Bude RO, Rubin JM, Adler RS. Power versus conventional color Doppler sonography: comparison in the depiction of normal intrarenal vasculature. Radiology 1994; 192: Krumme B, Blum U, Schwertfeger E et al. Diagnosis of renovascular disease by intra- and extrarenal Doppler scanning. Kidney Int 1966; 50: Hansen KJ, Tribble RW, Reavis SW et al. Renal duplex sonography: evaluation of clinical utility. J Vase Surg 1990; 12: Hoffmann U, Edwards JM, Carter S et al. Role of duplex scanning for the detection of atherosclerotic renal artery disease. Kidney Int 1991; 39: Nitzsche E, Grosser G, Rump C et al. Captopril- Nierenfunktionsszintigraphie (C-NFSZ) bei der Abklarung der arteriellen Hypertonie. Radiologe 1991; 31: Missouris CG, Allen CM, Balen FG, Buckenham T, Lees WR, MacGregor GA. Non-invasive screening for renal artery stenosis with ultrasound contrast enhancement. J Hypertens 1996; 14: Kliewer MA, Tupler RH, Carroll BA et al. Renal artery stenosis: analysis of Doppler waveform parameters and tardus-parvus pattern. Radiology 1993; 189: Bardelli M, Jensen G, Volkmann R, Aurell M. Non-invasive ultrasound assessment of renal artery stenosis by means of the Gosling pulsatility index. J Hypertens 1992; 10: Schwerk WB, Restrepo IK, Stellwaag M, Klose KJ, Schade- Brittinger C. Renal artery stenosis: grading with image-directed Doppler US evaluation of renal resistive index. Radiology 1994; 190: Stavros AT, Parker SH, Yakes WF et al. Segmental stenosis of the renal artery: pattern recognition of tardus and parvus abnormalities with duplex sonography. Radiology 1992; 184: Ochratoxin A: a new environmental factor which is toxic for the kidney? P. Simon 1, M. Godin 2 and J.-P. Fillastre 2 Service de Nephrologie, 'Hopital La Beauchee, Saint Brieuc; 2 H6pital Boisguillaume, Rouen, France Introduction Ochratoxin A, a toxic substance produced by several species of Aspergillus, especially by Aspergillus ochraceus and Penicillium verrucosum, is nephrotoxic in pigs [1] and experimental animals reviewed in [2]. This raises the possibility that ochratoxin A is also nephrotoxic in man. Ochratoxin A intoxication stems essentially from ingestion of contaminated food and drinks derived from cereals. In the last decade, data in favour of ochratoxin A nephrotoxicity in man have appeared [2-4]. However, although ochratoxin A nephrotoxicity has been proven in experimental animals, such proof is still lacking in man. In fact it is not easy to identify a single aetiological factor in human renal diseases, which develop over several decades. The purpose of this contribution is to review the data which suggest that ochratoxin A is definitely nephrotoxic in man. Correspondence and offprint requests to: Pierre Simon, Service de Nephrologie, Hopital La Beauchee, Saint Brieuc, France. What have we learned from animal experiments using ochratoxin A? There is no doubt that ochratoxin A is responsible for porcine nephropathy (in [2]). Evidence was adduced as early as 1928 that ochratoxin A induces renal injury in the pig [1]. Forty years later, Krogh [5] confirmed that pigs fed a diet contaminated by Penicillium verrucosum develop renal lesions. It was proposed that citrinin was the offending agent, in fact ochratoxin A was shown to be the most aggressive renal mycotoxin in the pig. When these animals received over several weeks a diet containing ochratoxin A-contaminated barley, they developed glycosuria, proteinuria, and polyuria with loss of renal concentrating capacity. Presence in the urine of N-acetyl glucosaminidase, leucine aminopeptidase, and lactate dehydrogenase indicated injury to proximal tubule cells. The pathological appearance of the kidney in porcine nephropathy was well analysed by Elling et al. [6] in The weight of the kidney is increased threefold.

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