- Email: [email protected]
Intrarenal doppler findings of upstream renal artery stenosis: A preliminary report
Ultrasound in Med. & Biol. Vol. 19, No. 1, pp. 3-12, 1993 Printed in the USA
0301-5629/93 $6.00 + .00 © 1993 Pergamon Press Ltd.
OOriginal Contribution INTRARENAL DOPPLER FINDINGS OF U P S T R E A M RENAL ARTERY STENOSIS: A PRELIMINARY REPORT S. S/]REYYA t~ZBEK, SUAT K . AYTAC, M . ILHAN ERDEN and N. U M M A N SANLIDiLEK The Department of Radiology, Ankara University, IBN-I Sina Hospital, Samanpazari, 06100 Ankara, Turkey (Received 10 February 1992;infinal form 27 July 1992) Abstract--To diagnose 60% or greater diameter-reducing stenosis of the renal artery (RAS), color Doppler imaging (CDI) and angiography were performed on 44 hypertensive and 16 normotensive cases. In this prospective, double-blind study we evaluated the related intrarenal waveform changes. In both the right and left kidneys of normotensive cases, at the level of interlobar arteries, the results indicated a symmetric finding in peak systolic/ end diastolic velocities (S/D), pulsatility index (PI) and resistive index (RI) ratios. The results in the stenotic kidneys among the hypertensive group indicated that index values were significantly lower in the stenotic kidneys than those of the contralateral kidneys, the kidneys of control and nonstenotic hypertensive cases. To quantify this observation we suggest "perfusion indexes," which require more studies on a greater number of hypertensive cases. It was concluded that measuring the index values of intrarenal arterial waveforms is easier and more accessible in diagnosing RAS than obtaining those of the main renal artery.
Key Words: Kidney, Renal artery, Renal artery obstruction, Hypertension, renovascular, Ultrasonic diagnosis, Ultrasonic Doppler effect, Renal circulation, Angiography, Angioplasty, transluminal, Color Doppler imaging, Doppler studies.
INTRODUCTION It is generally agreed that 3 to 6% of all patients referred to hospitals with hypertension have a renovascular pathology in their etiology (Franklin 1989). Renovascular hypertension is described as hypertension which is cured or improved after revascularization (Dunnick and Sfakianakis 1991). Although the percentage in the overall hypertensive population is small, the correctable and curable nature of the pathology has made the diagnosis ofrenovascular hypertension important. Up to now the gold standard used in diagnosing renovascular hypertension is renal arteriography, but the invasive nature and probable complications of the angiographic method have led many investigators to search for other screening techniques. Many researchers are interested in Doppler ultrasound (US) because of the invaluable hemodynamic information it supplies. Various criteria were used to detect renal artery stenosis (RAS) in the previous studies. The re-
Address correspondence to: Stiha Stireyya Ozbek, 1740 Sok., No.: 4/2, Orkide Apt., Daire: 3, Kar~iyaka, 35530 Izmir, Turkey.
ported sensitivity and specificity rates of these studies differ greatly. The reason for this discrepancy seems to be the varying percentage of technically successful examinations, the differing stenosis criteria and examination duration. In order to get a better idea of the performance of the Doppler US in diagnosing RAS, we started a study in our department. Besides some of the previously defined criteria, we intended to investigate the effect of an upstream stenosis on intrarenal arterial hemodynamics. MATERIALS AND METHODS
Between February 1991 and January 1992 we undertook a prospective study on the diagnosis of RAS. This study consisted of 44 referred hypertensive cases and 16 normotensive renal donors as a control group. We examined these 60 cases using both angiography and color Doppler imaging (CDI) within a designated 10-week period. The hypertensive cases were aged 13 to 57 years (mean, 35.0; 23 females, 21 males). The control group (potential renal donors) consisted of 13 females and 3 males, aged 18 to 63 years (mean, 42.0). One hypertensive patient was
4
Ultrasound in Medicineand Biology
clinically diagnosed with Takayasu's arteritis after the CDI examination. The examinations were performed with a Toshiba SSA-270A unit (Toshiba Corporation, Tochigiken, Japan). The 3.75 MHz convex and sector probes were routinely used with both spectral and color displays. Examinations were performed and interpreted by an experienced radiologist (SSO), who was supplied with all available clinical information, but without knowledge of the results of angiography. During the examinations, Doppler waveforms were obtained first from one interlobar and one segmental artery of each kidney, and then from the proximal orifice and the middle portion of each detected renal artery. From their respective Doppler tracings, the following velocities and values were determined: Peak systolic velocity (S), end diastolic velocity (D), mean velocity (M), the ratio of peak systolic to end diastolic velocities (S/D), resistive index [RI = (S D)/S], and pulsatility index [PI = (S - D)/M]. RI and PI values were calculated by using the Toshiba built-in software. The peak systolic velocity of the aorta at the level of the renal arteries was also measured in each case, in order to determine the renoaortic ratio (RAR). The length, parenchymal thickness and echogenicity were noted for each kidney. Throughout the study, a Doppler angle greater than 60 degrees was strictly avoided. Angular correction was made before each measurement. A sampling volume of 0.7-1.6 mm in axial and 3.3 mm in lateral dimension was used. The lowest pulsed-wave filter setting that would not cause an artifact, on a scale of 5 to 40, was used during the intrarenal arterial examinations. Patients were scanned in the contralateral decubitus position (left decubitus for the right kidney; right decubitus for the left kidney), and sometimes, in the supine position. To minimize respiration artifacts, all recordings were made during breath-holding periods. The examination duration was not limited, but an effort was made not to exceed the routine Doppler examination time limit. The subjects were also studied using intraarterial digital subtraction angiography (DSA). At our radiology department, intraarterial DSA studies are generally performed in two steps. In the first step, 20 mL of iohexol (Omnipaque-350; Nycomed, Oslo, Norway) (7.0 g of iodine) or iopromide (Ultravist-370; Schering, Berlin, Germany) (7.4 g of iodine) was injected nonselectively into the proximal abdominal aorta at a rate of 10 mL/s. In the second step, each of the renal arteries was catheterized, and 4 to 6 mL of the same contrast agents was injected at a rate of 2 to 3 mL/s, which varied according to the diameter of the artery, and the size of the parenchyma it perfused. In the -
Volume19, Number 1, 1993 cases with RAS, the luminal diameter in the region of the stenosis was compared with that in the adjacent proximal or distal normal renal artery, so the percentage of the diameter of the stenosis was estimated. Angiograms were interpreted without knowledge of the results of CDI. Significant RAS was accepted as a diameter-reducing stenosis of 60% or greater, which was also proposed by other researchers (Rittgers et al. 1985; Strandness 1990). We divided the 60 cases into three groups: normotensive potential renal donors as the normal control group, hypertensive patients with RAS in at least one kidney as the RAS(+) group and the hypertensive patients without RAS as the RAS(-) group. CDI was performed before and after Percutaneous Transluminal Renal Angioplasty (PTRA) in 5 RAS(+) patients. In order to analyze our data, we paired off the index values of the interlobar arteries. Thus, each pair consisted of the values of the right and left interlobar arteries of the same case. The S/D, RI, and PI values of each artery were compared to those of the other within each pair. We used a one-way analysis of variance, and student's t-test in comparing various indexes among groups. RESULTS Angiography demonstrated that 16 kidneys (13%) were supplied by 2 or more arteries. The number of total accessory arteries was 19. Nine kidneys were shown to have RAS. Among the 9 kidneys, 7 were shown to have stenosis in the main renal artery and 1 in the segmental artery. The remaining kidney was demonstrated to have an occluded left renal artery. Thirty-five hypertensive patients had normal renal angiography results or a RAS causing less than 60% reduction in diameter. Angiograms of all potential donors were normal. None of the subjects in the study had a renal arteriogram that suggested renal arteriovenous malformation (AVM). The average CDI examination time per kidney was 23.5 min, varying from 10 to 50 min. The detection and Doppler analysis of intrarenal arteries took an average of 10.7 min per kidney, varying from 5 to 35 min, which is 46% of the total examination time per kidney. The visualization of the intrarenal arteries was facilitated by the added capability of color flow imaging. Doppler waveforms were obtained from a segmental artery in 115 (96%) kidneys, and from an interlobar artery in 119 (99%) kidneys. For this reason, segmental artery values were not analyzed statistically. The only kidney with renal artery occlusion was seen to have intrarenal arterial signals, possibly
Intrarenal Doppler findings of RAS • S. SIAREYYA(~ZBEKel al. through a collateral circulation. The single case with intrarenal stenosis was excluded because of the unique characteristics it showed during the analysis of the data obtained from intrarenal arteries. Table 1 shows the m e a n S/D, RI, and PI values o f interlobar arteries in the control group, R A S ( - ) group, and RAS(+) group, together with the patient with occlusion. There was no significant difference in S/D, RI or PI values a m o n g the right and left kidneys of the control group or R A S ( - ) group. On the other hand, three index values of the stenotic kidneys were significantly lower than those of the contralateral kidneys (p < 0.01 for interlobar S/D, p < 0.001 for RI and PI). There was no significant difference in S/D, RI, and PI values a m o n g the right kidneys of the control group, R A S ( - ) group, and the contralateral kidneys of the RAS(+) group. However, the index values of the stenotic kidneys in the RAS(+) group were significantly lower than those of the control and R A S ( - ) groups (p < 0.001) (Figs. 1 and 2). Although, according to our observations, the probability of an upstream RAS varied inversely with interlobar artery S/D, RI or PI values (Proportion 1), we realized that there were also R A S ( - ) hypertensives, who had bilaterally low index values compared to those of the control group and other nonstenotic hypertensives. The patient with Takayasu's arteritis especially had very low index values. That bilateral very low S/D, RI, and PI values indicate renal ischemia needs further study. In the control and R A S ( - ) groups, the symmetric distribution of S/D, RI and PI values of the right and left segmental and interlobar arteries of the same subject was remarkable. This finding is in accordance with the observations of other researchers (Gottlieb et al. 1989; Platt et al. 1989). In order to mention the clear a s y m m e t r y of the index values of the RAS(+) group, and exclude low but symmetric values in the R A S ( - ) group, we divided each higher index value (A) by the lower value
5
(B) of the interlobar arteries in the same case, when both of the values were available. The ratios gave the degree of s y m m e t r y o f the values in each interlobar artery pair. The greater the ratio was, the m o r e asymmetric the index values were. According to our observations, the probability o f an upstream stenosis varied directly with that ratio ( A / B ) (Proportion 2). The m e a n values of these ratios were 1.09 _ 0.05, 1.11 +_ 0.10 and 1.46 _+0.25 ofinterlobar artery S/D values in control, R A S ( - ) and RAS(+) groups, respectively. The m e a n values of RI ratios were 1.06 + 0.04, 1.10 _+ 0.13 and 1.47 +__0.32, and the m e a n values o f PI ratios were 1.09 + 0.06, 1.13 + 0.12 and 1.71 +_ 0.50 in control, R A S ( - ) and RAS(+) groups, respectively. The ratio values o f all three indexes in the RAS(+) group were significantly greater than those of the other two groups (p < 0.001), while the ratios in the control and R A S ( - ) group did not show a significant difference between each other. When we combined Proportions 1 and 2, we got another proportion, which was the probability of an upstream stenosis directly proportional to A divided by B square, where A is the larger and B is the smaller index value derived from symmetric arteries of the same person. Using the formula below we calculated three new indexes for each pair of intedobar arteries, which we called "systolodiastolic perfusion index" (SPI), "resistive perfusion index" (RPI), and "pulsatile perfusion index" (PPI). In this way, we obtained three new index values for each case.
SPI -
(S/D)A [(S/D)]B] 2 '
RPI-
RIA (Ris)2 '
PPI-
PIA (pin)2 "
Table 1. Calculated parameters of interlobar arteries of the kidneys in the study.
Control Right Left RAS(-) Right Left RAS(+) Sten. Contr.
S/D
RI
PI
2.44 _+0.19 (n = 16) 2.38 +_0.17 (n = 16)
0.59 _+0.04 (n - 16) 0.58 _+0.03 (n - 16)
0.93 _+0.09 (n = 16) 0.90 _+0.08 (n = 16)
2.43 _+0.37 (n - 34) 2.41 _+0.45 (n = 34)
0.58 _+0.06 (n - 34) 0.57 +_0.07 (n = 34)
0.92 _+0.17 (n = 34) 0.90 +_0.17 (n = 34)
1.77 _+0.26 (n - 8) 2.51 _+0.51 (n = 8)
0.42 _+0.09 (n = 8) 0.60 +_0.07 (n = 8)
0.59 _+0.14 (n = 8) 0.97 +_0.18 (n = 8)
Note: Values are mean +_standard deviation. Sten. = stenotic kidney; Contr. = contralateral kidney; n = number of cases.
6
Ultrasound in Medicineand Biology
Volume19, Number 1, 1993
Fig. 1. Transverse sonogram of left kidney. Segmental arterial Doppler signals in a patient with left RAS. S/D = 1.56, RI = 0.36, PI = 0.44. Table 2 shows the mean perfusion index values for each group. There was no significant difference among any of these values of the control and R A S ( - ) groups. However, all the index values in the RAS(+) group were significantly higher than those of the control and R A S ( - ) groups (p < 0.001). The n u m b e r of cases in this preliminary study was limited, so we did not search for exact cut-off points of each perfusion index. However, our limited experience enables us to suggest that 0.70-0.80 SPI, 2.60-2.70 RPI, and 2.10-2.30 PPI seem to be the rough lower limits for the kidneys with RAS.
The only case that had an intrarenal RAS was determined as having no RAS at the first CDI examination. Angiographically, she was shown to have a greater than 60% diameter-reducing stenosis in the segmental artery, which perfuses the upper half of the right kidney (Fig. 3). As a unique model, the patient was examined with CDI again (Figs. 4 and 5). Table 3 shows the S/D, RI, PI values of the segmental and interlobar arteries in the left kidney, and in the upper and lower halves of the right kidney. When the values of the upper half and the contralateral kidney were compared, SPI, RPI, and PPI were, respectively, 0.76,
Fig. 2. Coronal sonogram of right kidney. Doppler signals from an interlobar artery. The artery of the kidney was significantly stenosed. S/D = 1.50, RI = 0.33, PI = 0.53.
Intrarenal Doppler findings of RAS • S. SOREYYAOZBEKet aL Table 2. Perfusion index values of interlobar arteries.
SPI RPI PPI
Control
RAS(-)
RAS(+)
0.47 + 0.03 (n = 16) 1.88 + 0.10 (n = 16) 1.24 + 0.13 (n = 16)
0.51 _+0.16 (n = 34) 1.93 + 0.34 (n = 34) 1.38 + 0.35 (n = 34)
0.85 _+0.24 (n = 8) 3.75 + 1.75 (n = 8) 3.24 _ 2.01 (n = 8)
Note: Valuesare mean _+standard deviation. SPI = systolodiastolicperfusionindex; RPI = ResistivePerfusion Index; PPI = Pulsatile Perfusion Index; n = number of cases. 3.86, and 3.45, for intedobar arteries. When the upper and the lower halves o f the right kidney were compared, SPI, RPI, and PPI were, respectively, 0.81, 4.08, and 3.51. All o f these index values were higher than the lower perfusion index limits for the stenotic kidneys suggested above. Five patients with RAS were examined 3-24 h (mean, 13.5) after PTRA. The pre- and post-PTRA S/D, RI and PI values are shown in Table 4. All of the post-PTRA S/D, RI and PI values were higher than the pre-PTRA values, while the post-PTRA perfusion index values were lower than the pre-PTRA values. The SPI, RPI and PPI values were 0.93 _+ 0.26, 4.02 _+ 2.05 and 3.82 _+ 2.39 in the pre-PTRA period, and 0.45 _+ 0.07, 1.83 _+ 0.23 and 1.16 _+ 0.31 in the postP T R A period, respectively (Fig. 6). DISCUSSION Although only a small percentage o f hypertensives have a renovascular etiological factor, the correctable nature of the disease is the reason which
makes its diagnosis important. The differential diagnosis of renovascular hypertension in the hypertensive population urged researchers to find a cheap, fast, reliable, and noninvasive technique. Owing to the information it supplies about vascular anatomy and hemodynamics, Doppler US has become the focus of interest in recent years. The results of the reported studies with the use o f the Doppler technique in diagnosing RAS are highly variable. One group of researchers reported promising results with sensitivity rates of 83-89%, and specificity rates of 73-97% (Avasthi et al. 1984; Rittgers et al. 1985; Strandness 1990). On the other hand, another group had disappointing rates of sensitivity (0%), and specificity (3750%) (Berland et al. 1990; Desberg et al. 1990). The main reason for the poor results in the latter group was suggested as being the difficulty of demonstrating the deep lying renal arteries. In fact, the percentage of technically adequate examinations has never been reported as greater than 90%, mostly being between 50% and 90% (Berland et al. 1990; Desberg et al. 1990; Greene et al. 1987; Hawkins et al. 1989).
Fig. 3. Intraarterial digital substraction angiogram of right kidney. Significant stenosis of the segmental branch perfusing the upper half of the kidney. The poor perfusion of the affected half relative to the lower half is obvious.
8
Ultrasound in Medicine and Biology
Volume19, Number 1, 1993
Fig. 4. Coronal sonogram of the same kidney shown in Fig. 3. Doppler signals from an interlobar artery in the upper half of the kidney. S/D = 1.50, RI = 0.33, PI = 0.41.
One of the great disadvantages o f Doppler US in scanning for RAS is the long examination duration. About 25-30 min per kidney were required for an adequate study (Desberg et al. 1990; Greene et al. 1981). We also had an average of 23.5 min per kidney, but we only spent approximately 46% (mean, 10.7 min) of this time in evaluating intrarenal arteries. In recent studies, peak systolic velocity and RAR of the main renal artery were generally accepted as the criteria for RAS (Avasthi et al. 1984; Berland et al.
1990; Desberg et al. 1990). Many investigators took a RAR ratio of 3.5 or greater as a RAS criterion (Berland et al. 1990; Desberg et al. 1990; Strandness 1990). Spectral broadening cannot be reliably quantified; therefore, although it is a typical finding o f RAS, it is not objective. All these above mentioned criteria were used to diagnose a stenosis in the main renal artery. They require the demonstration o f these arteries, which is not always technically possible. On the other hand, it is
Fig. 5. Normal Doppler signals from an interlobar artery in the lower half of the kidney shown in Figs. 3 and 4. S/D = 1.83, RI = 0.45, PI = 0.59.
Intrarenal Doppler findings of RAS • S. SUREYYAOZBEKet al. Table 3. Calculated variables of the case with intrarenal stenosis. Segmental artery
Right kidney Upper half Lower half Left kidney
Interlobar artery
S/D
RI
PI
S/D
RI
PI
1.39 1.77 1.78
0.28 0.44 0.44
0.41 0.57 0.58
1.50 1.83 1.71
0.33 0.45 0.42
0.41 0.59 0.45
theoretically impossible to detect intrarenal artery stenosis with the use of these criteria. Acceleration and acceleration time are the other criteria that have been studied for diagnosis of RAS. Handa et al. (1986) investigated the velocity waveforms of the renal artery and its segmental branches in renal hilum. Using these waveforms they described acceleration index and acceleration time, which they reported to be indicators of an upstream stenosis. Similar indirect changes of a significant proximal stenosis were described by Stavros at the Annual Meeting of the RSNA in 1990. According to our experience, acceleration parameters have relatively low reproducibility. "Early systolic notch," which was also described by Stavros (RSNA 1990) in normal segmental arteries, makes the measurement of acceleration and acceleration time more complicated. Some of these typical waveforms that we observe have a delayed second peak, which has a higher value than the initial one. In this case, it is controversial which one of the peaks should be used to measure acceleration and acceleration time. On the other hand, segmental and interlobar arteries do not always demonstrate "early systolic notch" in normal subjects. These waveforms have an initial slope up to peak, which is generally parabolic instead of being straight. In these cases, it is practically impossible to determine acceleration parameters, especially the "acceleration index" described by Handa et al. (1986). We noticed that intrarenal arterial waveforms dampen downstream to a significant RAS. While intrarenal arterial velocities are dependent on individual variations in systemic hemodynamics and anatomy, we do not think that low velocity values alone can be used as a criterion for RAS. S/D, RI, and PI values ofintrarenal arteries have been studied for the diagnosis of renal parenchymal disease, or to evaluate renal allograft dysfunction (Allen et al. 1988; Patriquin et al. 1989; Platt et al. 1990; Ritkin et al. 1987; Wan et al. 1988). In all these studies, the focus of attention was the upper normal thresholds of these indexes. Now, owing to our results, we suggest that the lower normal limits of these values also deserve the same interest and attention. S/D, RI,
9
and PI values ofintrarenal arteries in the stenotic kidneys were significantly lower than those of other kidneys. The same observation was made by comparing the two halves of the same kidney of a very typical case, where one kidney had a well-perfused lower half but, because of RAS, poorly perfused upper half. Low intrarenal RI values have also been reported in cases of renal AVM. However, this finding is limited to a specific area as other typical Doppler findings of AVM such as high-velocity intrarenal jets and arterialization of the draining veins, since AVM is a local pathological process (Middleton et al. 1989; Takebayashi et al. 1991). In cases of AVM, low resistivity is present in the supplying artery of the lesion, in contrast to the RAS(+) cases in our study where low S/D, RI and PI values were found downstream to the stenosis. The malformation can be clearly located with the help of pulsed-wave or color Doppler aliasing. CDI, in particular, facilitates the depiction of high-velocity intrarenal jets. None of the kidneys in the study was found to have the above mentioned Doppler findings or the angiographic evidence of AVM. The kidney with intrarenal arterial stenosis had a focal area of low-resistivity and high-velocity jets, but low resistivity was limited downstream to the lesion, and the draining vein was not arterialized. The Doppler waveform depends on vascular compliance and the presence of any disease upstream or downstream (Hoskins 1990). RI and PI reflect both distal and proximal hemodynamics (Greene et al. 1987). The waveform changes we observed might be caused by the decrease of vascular resistance in ischemic renal parenchyma and/or the direct physiological effect of stenosis on hemodynamics. The kidneys are capable of autoregulating renal blood flow and glomerular filtration rate within narrow limits. Autoregulatory responses are mediated by active adjustment of smooth muscle tone. The major site for autoregulatory resistance adjustment is preglomerular. At present, there are two hypotheses as potential mechanisms of renal autoregulation. The macula densa hypothesis invokes the tubuloglomeru-
T a b l e 4. C o m p a r i s o n o f S/D, RI a n d PI values before a n d after P T R A in R A S ( + ) patients.
Stenotic kidney Pre-PTRA Post-PTRA Contralateral kidney Pre-PTRA Post-PTRA
S/D
RI
PI
1.77 _+ 0.28 2.61 +_ 0.63
0.42 _+0.10 0.60 _+0.08
0.57 + 0.17 1.00 _+0.26
2.84 + 0.64 2.60 _+ 0.34
0.63 + 0.10 0.61 _+0.05
1.03 + 0.25 1.06 + 0.21
Note: PTRA - Percutaneous Transluminal Renal Angioplasty,
lO
Ultrasound in Medicineand Biology
Volume 19, Number 1, 1993
'r
INDEX VALUE
4
::::::::::::::::::::::::::::::::::::::
.......
PREPTRA
PO8TPTRA 8PI
~
RPI
I
PPI
Fig. 6. Comparison of perfusion indexes before and after PTRA in patients with RAS. lar feedback (TGF) mechanism. It predicts that disturbances that increase tubular fluid flow will elicit vasoconstriction, whereas decreases in flow, as in the example of a significant RAS, will cause vasodilation, mainly in afferent arterioles. The myogenic hypothesis imparts to renal vascular smooth muscle the ability to sense changes in vessel wall tension and to respond with appropriate adjustments in tone. For example, an increase in wall tension, occurring as a passive response to an elevation in arterial pressure, is thought to stimulate a sensor element and initiate a chain of events resulting in vascular smooth muscle contraction. Interlobular and afferent arterioles have been reported to exhibit myogenic responses to change in wall tension (Navar et al. 1989). Schwietzer and Gertz (1979) demonstrated the preglomerular vascular resistance changes in clamped and unclamped kidneys of two-kidney Goldblatt rats by using micropuncture techniques. The preglomerular vascular resistance increased by 51% in unclamped kidneys, and 21% in clamped kidneys compared to that of controls. Although there seems to be a discrepancy about the relative preglomerular vascular resistances of stenotic and normal kidneys between the above mentioned hypotheses and the results by Schwietzer and Gertz (1979), all are in agreement that a reduction in preglomerular vascular resistance exists in stenotic kidney compared to that of the contralateral kidney. This is probably reflected in RI, which has been shown to be a good indicator of renovascular resistance with experimental studies (Norris and Barnes 1984). The same is also true for PI and S/D, which are all directionally similar, although quantitatively different.
When time-varying flow passes through a stenosis, its pulsatility is affected. Resistance ofstenosis and compliance of downstream arteries combine to absorb high-frequency components of the pressure pulse, resulting in a less pulsatile flow downstream from a stenotic lesion (Burns 1988). This is exactly what we observed in the Doppler waveforms of the segmental and interlobar arteries in significantly stenotic kidneys. For all of the perfusion indexes, there was no statistically significant difference between the control and RAS(-) groups, whereas all indexes were higher in the RAS(+) group than those of the other two groups. Since there was not any case of AVM in our series, we could not obtain associated perfusion index values. In cases of renal AVM, perfusion index values could also be expected to be high, as S/D, RI and PI values of the supplying artery would be significantly lower than those of the contralateral kidney. However, AVM could be easily differentiated from RAS with the help of the typical Doppler findings mentioned above. The S/D, RI and PI values of all RAS(+) patients rose to normal values after PTRA. This finding is in accordance with those of Soulen (RSNA 1991). The perfusion indexes also returned to normal lower values after the procedure. We think that low S/D, RI and PI values or asymmetric distribution of these indexes alone cannot be depended on as a criterion of significant RAS, but a combination, such as perfusion indexes, should be used. Low S/D, RI and PI values probably demonstrate an insufficient blood supply, due to significant RAS or to central reasons. The latter was observed in the patient with Takayasu's arteritis, who had a signifi-
Intrarenal Doppler findings of RAS • S. SOREYYAQ)ZBEKel aL
cant aortic stenosis proximal to the renal arteries. Bilateral low indexes with irregular waveforms were very remarkable. Accessory renal arteries were mentioned by other authors as a factor that limits the accuracy of Doppler US in diagnosing RAS (Berland et al. 1990; Desberg et al. 1990; Eidt et al. 1990; Greene et al. 1987; Robertson et al. 1988), Deriving Doppler signals from the parenchymal areas perfused by accessory arteries seems to be easier and more applicable than demonstrating them. For this purpose, it would be better to sample and analyze two or more interlobar arteries from different parts of every kidney instead of one segmental and one interlobar artery, as we did in our study. The index values should then be compared with those obtained from the identical region of the contralateral kidney. The same technique may have a greater chance of revealing a renal artery branch or segmental artery stenosis, which are impossible to detect by scanning the main renal arteries only. As a matter of fact, SPI, RPI, and PPI values of the patient with intrarenal stenosis, obtained by comparing the values of the stenotic upper half of the kidney with those of either the lower half of the kidney with those of either the lower half of the same kidney or contralateral kidney, were all in the pathological range. It is necessary to have carefully controlled prospective studies on the waveform changes we observed, and perfusion indexes we suggested, with a larger number of RAS(+) patients. In fact, we have begun such a new study in our department. However, the results and findings of this preliminary study with a limited number of RAS(+) patients are quite remarkable. Accordingly, we suggest a new method in the diagnosis of RAS with which the factors limiting the routine use of Doppler US, such as tympanites, obesity or long examination duration, may be overcome. In our opinion, in addition to the main renal arteries, renal parenchymal arteries should be examined for the indirect findings of an upstream RAS. SUMMARY In this prospective, double-blind study we evaluated the intrarenal arterial waveforms in the kidneys of normal and hypertensive cases. In both the right and left kidneys of normal and hypertensive cases without a significant renal artery stenosis, the results indicated a symmetric finding in all three S/D, PI and RI ratios. All these index values were significantly lower in the stenotic kidneys than those of the contralateral normal kidneys, the kidneys of hypertensive cases without renovascular disease and control subjects. To
11
quantify this observation we suggest "perfusion indexes," which require more studies on a greater number of hypertensive cases. It was concluded that measuring the index values of intrarenal arterial waveforms is easier and more accessible in diagnosing RAS than obtaining the velocity waveforms of the main renal artery. REFERENCES Allen, K. S.; Jorkasky, D. K.; Arger, P. H.; Velchik, M. G.; Grumbach, K. Renal allografts: Prospective analysis of Doppler sonography. Radiology 169:371-376; 1988. Avasthi, P. S.; Voyles, W. F.; Greene, E. R. Noninvasive diagnosis of renal artery stenosis by echo-Doppler velocimetry. Kidney Int. 25:824-829; 1984. Berland, L. L.; Koslin, D. B.; Routh, W. D.; Keller, F. S. Renal artery stenosis: Prospective evaluation of diagnosis with color duplex US compared with angiography (work in progress). Radiology 174:421-423; 1990. Bums, P. N. Hemodynamics. In: Taylor, K. J. W.; Burns, P. N.; Wells, P. N. T., eds. Clinical applications of Doppler ultrasound. New York: Raven Press; 1988:46-75. Desberg, A. L.; Paushter, D. M.; Lammert, G. K.; Hale, J. C.; Troy, R. B. Renal artery stenosis: Evaluation with color Doppler flow imaging. Radiology 177:749-753; 1990. Dunnick, N. R.; Sfakianakis, G. N. Screening for renovascular hypertension. Radiol. Clin. North Am. 29:497-510; 1991. Eidt, J. F.; Harward, T.; Cook, J. M.; Kahn, M. B.; Troillet, R. Current status of duplex Doppler ultrasound in the examination of the abdominal vasculature. Am. J. Surg. 160:604-609:1990. Franklin, S. S. Renovascular hypertension. In: Massry, S. G.; Glassock, R. J., eds. Textbook of nephrology. 2nd ed. Baltimore: Williams & Wilkins; 1989:1081-1090. Gottlieb, R. H.; Luhmann, K., IV; Pates, R. P. Duplex ultrasound evaluation of normal native kidneys and native kidneys with urinary tract obstruction. J. Ultrasound Med. 8:609-611 ; 1989. Greene, E. R.; Avasthi, P. S.; Hodges, J. W. Noninvasive Doppler assessment of renal artery stenosis and hemodynamics. J. Clin. Ultrasound 15:653-659; 1987. Greene, E. R.; Venters, M. D.; Avasthi, P. S.; Conn, R. L.; Jahnke, R. W. Noninvasive characterization of renal artery blood flow. Kidney Int. 20:523-529:1981. Handa, N.; Fukunaga, R.; Uehara, A.; Etani H.; Yoneda, S. EchoDoppler velocimeter in the diagnosis of hypertensive patients: The renal artery Doppler technique. Ultrasound Med. Biol. 12:945-952: 1986. Hawkins, P. G.; McKnoulty, L. M.; Gordon, R. D.; Klemm, S. A.; Tunny, T. J. Noninvasive renal artery duplex ultrasound and computerized nuclear renography to screen for and follow progress in renal artery stenosis. J. Hypertens. 7 (Suppl. 6):S184S185; 1989. Hoskins, R. Quantitative techniques in arterial Doppler ultrasound. Clin. Phys. Physiol. Meas. 11 (Suppl. A):75-80; 1990. Middleton, W. D.; Kellman, G. M.; Melson, G. L.; Madrazo, B. L. Postbiopsy renal transplant arteriovenous fistulas: Color Doppler US characteristics. Radiology 171:253-257; 1989. Navar, L. G.; Carmines, P. K.; Paul, R. V. Renal circulation. In: Massry, S. G.; Glassock R. J., eds. Textbook of nephrology. 2nd ed. Baltimore: Williams & Wilkins; 1989:43-53. Norris, C. S.; Barnes, R. W. Renal artery flow velocity analysis: A sensitive measure of experimental and clinical renovascular resistance. J. Surg. Res. 36:230-236; 1984. Patriquin, H. B.; O'Reagan, S.; Robitaille, P.; Paltiel, H. Hemolytic-uremic syndrome: lntrarenal arterial Doppler patterns as a useful guide to therapy. Radiology 172:625-628; 1989. Platt, J. F.; Ellis, J. H.; Rubin, J. M.; DiPietro, M. A.; Sedman, A. B.
12
Ultrasound in Medicine and Biology
Intrarenal arterial Doppler sonography in patients with nonobstructive renal disease: Correlation of resistive index with biopsy findings. Am. J. Roentg. 154:1223-1227; 1990. Piatt, J. F.; Rubin, J. M.; Ellis, J. H. Distinction between obstructive and nonobstructive pyelocaliectasis with duplex Doppler sonography. Am. J. Roentg. 153:997-1000; 1989. Rilkin, M. D.; Needleman, L.; Pasto, M. E.; Kurtz, A. B.; Foy, P. M. Evaluation of renal transplant rejection by duplex Doppler examination: Value of the resistive index. Am. J. Roentg. 148:759-762; 1987. Rittgers, S. E.; Norris, C. S.; Barnes, R. W. Detection of renal artery stenosis: Experimental and clinical analysis of velocity waveforms. Ultrasound Med. Biol. 11:523-531; 1985. Robertson, R.; Murphy, A.; Dubbins, P. A. Renal artery stenosis:
Volume 19, Number 1, 1993 The use of duplex ultrasound as a screening technique. Br. J. Radiol. 61:196-201; 1988. Schwietzer, G.; Gertz, K. H. Changes of hemodynamics and glomerular ultrafiltration in renal hypertension of rats. Kidney Int. 15:134-143; 1979. Strandness, D. E. Duplex scanning in diagnosis of renovascular hypertension. Surg. Clin. North Am. 70:109-117; 1990. Takebayashi, S.; Aida, N.; Matsui, K. Arteriovenous malformations of the kidneys: Diagnosis and follow-up with color Doppler sonography in six patients. Am. J. Roentg. 157:991995; 1991. Wan, S. K. H.; Ferguson, C. J.; Cochlin, D. L. L.; Evans, C.; Griffiths, D. F. R. Duplex Doppler ultrasound in the diagnosis of acute renal allografi rejection. Clin. Radiol. 40:573-576; 1988.
0301-5629/93 $6.00 + .00 © 1993 Pergamon Press Ltd.
OOriginal Contribution INTRARENAL DOPPLER FINDINGS OF U P S T R E A M RENAL ARTERY STENOSIS: A PRELIMINARY REPORT S. S/]REYYA t~ZBEK, SUAT K . AYTAC, M . ILHAN ERDEN and N. U M M A N SANLIDiLEK The Department of Radiology, Ankara University, IBN-I Sina Hospital, Samanpazari, 06100 Ankara, Turkey (Received 10 February 1992;infinal form 27 July 1992) Abstract--To diagnose 60% or greater diameter-reducing stenosis of the renal artery (RAS), color Doppler imaging (CDI) and angiography were performed on 44 hypertensive and 16 normotensive cases. In this prospective, double-blind study we evaluated the related intrarenal waveform changes. In both the right and left kidneys of normotensive cases, at the level of interlobar arteries, the results indicated a symmetric finding in peak systolic/ end diastolic velocities (S/D), pulsatility index (PI) and resistive index (RI) ratios. The results in the stenotic kidneys among the hypertensive group indicated that index values were significantly lower in the stenotic kidneys than those of the contralateral kidneys, the kidneys of control and nonstenotic hypertensive cases. To quantify this observation we suggest "perfusion indexes," which require more studies on a greater number of hypertensive cases. It was concluded that measuring the index values of intrarenal arterial waveforms is easier and more accessible in diagnosing RAS than obtaining those of the main renal artery.
Key Words: Kidney, Renal artery, Renal artery obstruction, Hypertension, renovascular, Ultrasonic diagnosis, Ultrasonic Doppler effect, Renal circulation, Angiography, Angioplasty, transluminal, Color Doppler imaging, Doppler studies.
INTRODUCTION It is generally agreed that 3 to 6% of all patients referred to hospitals with hypertension have a renovascular pathology in their etiology (Franklin 1989). Renovascular hypertension is described as hypertension which is cured or improved after revascularization (Dunnick and Sfakianakis 1991). Although the percentage in the overall hypertensive population is small, the correctable and curable nature of the pathology has made the diagnosis ofrenovascular hypertension important. Up to now the gold standard used in diagnosing renovascular hypertension is renal arteriography, but the invasive nature and probable complications of the angiographic method have led many investigators to search for other screening techniques. Many researchers are interested in Doppler ultrasound (US) because of the invaluable hemodynamic information it supplies. Various criteria were used to detect renal artery stenosis (RAS) in the previous studies. The re-
Address correspondence to: Stiha Stireyya Ozbek, 1740 Sok., No.: 4/2, Orkide Apt., Daire: 3, Kar~iyaka, 35530 Izmir, Turkey.
ported sensitivity and specificity rates of these studies differ greatly. The reason for this discrepancy seems to be the varying percentage of technically successful examinations, the differing stenosis criteria and examination duration. In order to get a better idea of the performance of the Doppler US in diagnosing RAS, we started a study in our department. Besides some of the previously defined criteria, we intended to investigate the effect of an upstream stenosis on intrarenal arterial hemodynamics. MATERIALS AND METHODS
Between February 1991 and January 1992 we undertook a prospective study on the diagnosis of RAS. This study consisted of 44 referred hypertensive cases and 16 normotensive renal donors as a control group. We examined these 60 cases using both angiography and color Doppler imaging (CDI) within a designated 10-week period. The hypertensive cases were aged 13 to 57 years (mean, 35.0; 23 females, 21 males). The control group (potential renal donors) consisted of 13 females and 3 males, aged 18 to 63 years (mean, 42.0). One hypertensive patient was
4
Ultrasound in Medicineand Biology
clinically diagnosed with Takayasu's arteritis after the CDI examination. The examinations were performed with a Toshiba SSA-270A unit (Toshiba Corporation, Tochigiken, Japan). The 3.75 MHz convex and sector probes were routinely used with both spectral and color displays. Examinations were performed and interpreted by an experienced radiologist (SSO), who was supplied with all available clinical information, but without knowledge of the results of angiography. During the examinations, Doppler waveforms were obtained first from one interlobar and one segmental artery of each kidney, and then from the proximal orifice and the middle portion of each detected renal artery. From their respective Doppler tracings, the following velocities and values were determined: Peak systolic velocity (S), end diastolic velocity (D), mean velocity (M), the ratio of peak systolic to end diastolic velocities (S/D), resistive index [RI = (S D)/S], and pulsatility index [PI = (S - D)/M]. RI and PI values were calculated by using the Toshiba built-in software. The peak systolic velocity of the aorta at the level of the renal arteries was also measured in each case, in order to determine the renoaortic ratio (RAR). The length, parenchymal thickness and echogenicity were noted for each kidney. Throughout the study, a Doppler angle greater than 60 degrees was strictly avoided. Angular correction was made before each measurement. A sampling volume of 0.7-1.6 mm in axial and 3.3 mm in lateral dimension was used. The lowest pulsed-wave filter setting that would not cause an artifact, on a scale of 5 to 40, was used during the intrarenal arterial examinations. Patients were scanned in the contralateral decubitus position (left decubitus for the right kidney; right decubitus for the left kidney), and sometimes, in the supine position. To minimize respiration artifacts, all recordings were made during breath-holding periods. The examination duration was not limited, but an effort was made not to exceed the routine Doppler examination time limit. The subjects were also studied using intraarterial digital subtraction angiography (DSA). At our radiology department, intraarterial DSA studies are generally performed in two steps. In the first step, 20 mL of iohexol (Omnipaque-350; Nycomed, Oslo, Norway) (7.0 g of iodine) or iopromide (Ultravist-370; Schering, Berlin, Germany) (7.4 g of iodine) was injected nonselectively into the proximal abdominal aorta at a rate of 10 mL/s. In the second step, each of the renal arteries was catheterized, and 4 to 6 mL of the same contrast agents was injected at a rate of 2 to 3 mL/s, which varied according to the diameter of the artery, and the size of the parenchyma it perfused. In the -
Volume19, Number 1, 1993 cases with RAS, the luminal diameter in the region of the stenosis was compared with that in the adjacent proximal or distal normal renal artery, so the percentage of the diameter of the stenosis was estimated. Angiograms were interpreted without knowledge of the results of CDI. Significant RAS was accepted as a diameter-reducing stenosis of 60% or greater, which was also proposed by other researchers (Rittgers et al. 1985; Strandness 1990). We divided the 60 cases into three groups: normotensive potential renal donors as the normal control group, hypertensive patients with RAS in at least one kidney as the RAS(+) group and the hypertensive patients without RAS as the RAS(-) group. CDI was performed before and after Percutaneous Transluminal Renal Angioplasty (PTRA) in 5 RAS(+) patients. In order to analyze our data, we paired off the index values of the interlobar arteries. Thus, each pair consisted of the values of the right and left interlobar arteries of the same case. The S/D, RI, and PI values of each artery were compared to those of the other within each pair. We used a one-way analysis of variance, and student's t-test in comparing various indexes among groups. RESULTS Angiography demonstrated that 16 kidneys (13%) were supplied by 2 or more arteries. The number of total accessory arteries was 19. Nine kidneys were shown to have RAS. Among the 9 kidneys, 7 were shown to have stenosis in the main renal artery and 1 in the segmental artery. The remaining kidney was demonstrated to have an occluded left renal artery. Thirty-five hypertensive patients had normal renal angiography results or a RAS causing less than 60% reduction in diameter. Angiograms of all potential donors were normal. None of the subjects in the study had a renal arteriogram that suggested renal arteriovenous malformation (AVM). The average CDI examination time per kidney was 23.5 min, varying from 10 to 50 min. The detection and Doppler analysis of intrarenal arteries took an average of 10.7 min per kidney, varying from 5 to 35 min, which is 46% of the total examination time per kidney. The visualization of the intrarenal arteries was facilitated by the added capability of color flow imaging. Doppler waveforms were obtained from a segmental artery in 115 (96%) kidneys, and from an interlobar artery in 119 (99%) kidneys. For this reason, segmental artery values were not analyzed statistically. The only kidney with renal artery occlusion was seen to have intrarenal arterial signals, possibly
Intrarenal Doppler findings of RAS • S. SIAREYYA(~ZBEKel al. through a collateral circulation. The single case with intrarenal stenosis was excluded because of the unique characteristics it showed during the analysis of the data obtained from intrarenal arteries. Table 1 shows the m e a n S/D, RI, and PI values o f interlobar arteries in the control group, R A S ( - ) group, and RAS(+) group, together with the patient with occlusion. There was no significant difference in S/D, RI or PI values a m o n g the right and left kidneys of the control group or R A S ( - ) group. On the other hand, three index values of the stenotic kidneys were significantly lower than those of the contralateral kidneys (p < 0.01 for interlobar S/D, p < 0.001 for RI and PI). There was no significant difference in S/D, RI, and PI values a m o n g the right kidneys of the control group, R A S ( - ) group, and the contralateral kidneys of the RAS(+) group. However, the index values of the stenotic kidneys in the RAS(+) group were significantly lower than those of the control and R A S ( - ) groups (p < 0.001) (Figs. 1 and 2). Although, according to our observations, the probability of an upstream RAS varied inversely with interlobar artery S/D, RI or PI values (Proportion 1), we realized that there were also R A S ( - ) hypertensives, who had bilaterally low index values compared to those of the control group and other nonstenotic hypertensives. The patient with Takayasu's arteritis especially had very low index values. That bilateral very low S/D, RI, and PI values indicate renal ischemia needs further study. In the control and R A S ( - ) groups, the symmetric distribution of S/D, RI and PI values of the right and left segmental and interlobar arteries of the same subject was remarkable. This finding is in accordance with the observations of other researchers (Gottlieb et al. 1989; Platt et al. 1989). In order to mention the clear a s y m m e t r y of the index values of the RAS(+) group, and exclude low but symmetric values in the R A S ( - ) group, we divided each higher index value (A) by the lower value
5
(B) of the interlobar arteries in the same case, when both of the values were available. The ratios gave the degree of s y m m e t r y o f the values in each interlobar artery pair. The greater the ratio was, the m o r e asymmetric the index values were. According to our observations, the probability o f an upstream stenosis varied directly with that ratio ( A / B ) (Proportion 2). The m e a n values of these ratios were 1.09 _ 0.05, 1.11 +_ 0.10 and 1.46 _+0.25 ofinterlobar artery S/D values in control, R A S ( - ) and RAS(+) groups, respectively. The m e a n values of RI ratios were 1.06 + 0.04, 1.10 _+ 0.13 and 1.47 +__0.32, and the m e a n values o f PI ratios were 1.09 + 0.06, 1.13 + 0.12 and 1.71 +_ 0.50 in control, R A S ( - ) and RAS(+) groups, respectively. The ratio values o f all three indexes in the RAS(+) group were significantly greater than those of the other two groups (p < 0.001), while the ratios in the control and R A S ( - ) group did not show a significant difference between each other. When we combined Proportions 1 and 2, we got another proportion, which was the probability of an upstream stenosis directly proportional to A divided by B square, where A is the larger and B is the smaller index value derived from symmetric arteries of the same person. Using the formula below we calculated three new indexes for each pair of intedobar arteries, which we called "systolodiastolic perfusion index" (SPI), "resistive perfusion index" (RPI), and "pulsatile perfusion index" (PPI). In this way, we obtained three new index values for each case.
SPI -
(S/D)A [(S/D)]B] 2 '
RPI-
RIA (Ris)2 '
PPI-
PIA (pin)2 "
Table 1. Calculated parameters of interlobar arteries of the kidneys in the study.
Control Right Left RAS(-) Right Left RAS(+) Sten. Contr.
S/D
RI
PI
2.44 _+0.19 (n = 16) 2.38 +_0.17 (n = 16)
0.59 _+0.04 (n - 16) 0.58 _+0.03 (n - 16)
0.93 _+0.09 (n = 16) 0.90 _+0.08 (n = 16)
2.43 _+0.37 (n - 34) 2.41 _+0.45 (n = 34)
0.58 _+0.06 (n - 34) 0.57 +_0.07 (n = 34)
0.92 _+0.17 (n = 34) 0.90 +_0.17 (n = 34)
1.77 _+0.26 (n - 8) 2.51 _+0.51 (n = 8)
0.42 _+0.09 (n = 8) 0.60 +_0.07 (n = 8)
0.59 _+0.14 (n = 8) 0.97 +_0.18 (n = 8)
Note: Values are mean +_standard deviation. Sten. = stenotic kidney; Contr. = contralateral kidney; n = number of cases.
6
Ultrasound in Medicineand Biology
Volume19, Number 1, 1993
Fig. 1. Transverse sonogram of left kidney. Segmental arterial Doppler signals in a patient with left RAS. S/D = 1.56, RI = 0.36, PI = 0.44. Table 2 shows the mean perfusion index values for each group. There was no significant difference among any of these values of the control and R A S ( - ) groups. However, all the index values in the RAS(+) group were significantly higher than those of the control and R A S ( - ) groups (p < 0.001). The n u m b e r of cases in this preliminary study was limited, so we did not search for exact cut-off points of each perfusion index. However, our limited experience enables us to suggest that 0.70-0.80 SPI, 2.60-2.70 RPI, and 2.10-2.30 PPI seem to be the rough lower limits for the kidneys with RAS.
The only case that had an intrarenal RAS was determined as having no RAS at the first CDI examination. Angiographically, she was shown to have a greater than 60% diameter-reducing stenosis in the segmental artery, which perfuses the upper half of the right kidney (Fig. 3). As a unique model, the patient was examined with CDI again (Figs. 4 and 5). Table 3 shows the S/D, RI, PI values of the segmental and interlobar arteries in the left kidney, and in the upper and lower halves of the right kidney. When the values of the upper half and the contralateral kidney were compared, SPI, RPI, and PPI were, respectively, 0.76,
Fig. 2. Coronal sonogram of right kidney. Doppler signals from an interlobar artery. The artery of the kidney was significantly stenosed. S/D = 1.50, RI = 0.33, PI = 0.53.
Intrarenal Doppler findings of RAS • S. SOREYYAOZBEKet aL Table 2. Perfusion index values of interlobar arteries.
SPI RPI PPI
Control
RAS(-)
RAS(+)
0.47 + 0.03 (n = 16) 1.88 + 0.10 (n = 16) 1.24 + 0.13 (n = 16)
0.51 _+0.16 (n = 34) 1.93 + 0.34 (n = 34) 1.38 + 0.35 (n = 34)
0.85 _+0.24 (n = 8) 3.75 + 1.75 (n = 8) 3.24 _ 2.01 (n = 8)
Note: Valuesare mean _+standard deviation. SPI = systolodiastolicperfusionindex; RPI = ResistivePerfusion Index; PPI = Pulsatile Perfusion Index; n = number of cases. 3.86, and 3.45, for intedobar arteries. When the upper and the lower halves o f the right kidney were compared, SPI, RPI, and PPI were, respectively, 0.81, 4.08, and 3.51. All o f these index values were higher than the lower perfusion index limits for the stenotic kidneys suggested above. Five patients with RAS were examined 3-24 h (mean, 13.5) after PTRA. The pre- and post-PTRA S/D, RI and PI values are shown in Table 4. All of the post-PTRA S/D, RI and PI values were higher than the pre-PTRA values, while the post-PTRA perfusion index values were lower than the pre-PTRA values. The SPI, RPI and PPI values were 0.93 _+ 0.26, 4.02 _+ 2.05 and 3.82 _+ 2.39 in the pre-PTRA period, and 0.45 _+ 0.07, 1.83 _+ 0.23 and 1.16 _+ 0.31 in the postP T R A period, respectively (Fig. 6). DISCUSSION Although only a small percentage o f hypertensives have a renovascular etiological factor, the correctable nature of the disease is the reason which
makes its diagnosis important. The differential diagnosis of renovascular hypertension in the hypertensive population urged researchers to find a cheap, fast, reliable, and noninvasive technique. Owing to the information it supplies about vascular anatomy and hemodynamics, Doppler US has become the focus of interest in recent years. The results of the reported studies with the use o f the Doppler technique in diagnosing RAS are highly variable. One group of researchers reported promising results with sensitivity rates of 83-89%, and specificity rates of 73-97% (Avasthi et al. 1984; Rittgers et al. 1985; Strandness 1990). On the other hand, another group had disappointing rates of sensitivity (0%), and specificity (3750%) (Berland et al. 1990; Desberg et al. 1990). The main reason for the poor results in the latter group was suggested as being the difficulty of demonstrating the deep lying renal arteries. In fact, the percentage of technically adequate examinations has never been reported as greater than 90%, mostly being between 50% and 90% (Berland et al. 1990; Desberg et al. 1990; Greene et al. 1987; Hawkins et al. 1989).
Fig. 3. Intraarterial digital substraction angiogram of right kidney. Significant stenosis of the segmental branch perfusing the upper half of the kidney. The poor perfusion of the affected half relative to the lower half is obvious.
8
Ultrasound in Medicine and Biology
Volume19, Number 1, 1993
Fig. 4. Coronal sonogram of the same kidney shown in Fig. 3. Doppler signals from an interlobar artery in the upper half of the kidney. S/D = 1.50, RI = 0.33, PI = 0.41.
One of the great disadvantages o f Doppler US in scanning for RAS is the long examination duration. About 25-30 min per kidney were required for an adequate study (Desberg et al. 1990; Greene et al. 1981). We also had an average of 23.5 min per kidney, but we only spent approximately 46% (mean, 10.7 min) of this time in evaluating intrarenal arteries. In recent studies, peak systolic velocity and RAR of the main renal artery were generally accepted as the criteria for RAS (Avasthi et al. 1984; Berland et al.
1990; Desberg et al. 1990). Many investigators took a RAR ratio of 3.5 or greater as a RAS criterion (Berland et al. 1990; Desberg et al. 1990; Strandness 1990). Spectral broadening cannot be reliably quantified; therefore, although it is a typical finding o f RAS, it is not objective. All these above mentioned criteria were used to diagnose a stenosis in the main renal artery. They require the demonstration o f these arteries, which is not always technically possible. On the other hand, it is
Fig. 5. Normal Doppler signals from an interlobar artery in the lower half of the kidney shown in Figs. 3 and 4. S/D = 1.83, RI = 0.45, PI = 0.59.
Intrarenal Doppler findings of RAS • S. SUREYYAOZBEKet al. Table 3. Calculated variables of the case with intrarenal stenosis. Segmental artery
Right kidney Upper half Lower half Left kidney
Interlobar artery
S/D
RI
PI
S/D
RI
PI
1.39 1.77 1.78
0.28 0.44 0.44
0.41 0.57 0.58
1.50 1.83 1.71
0.33 0.45 0.42
0.41 0.59 0.45
theoretically impossible to detect intrarenal artery stenosis with the use of these criteria. Acceleration and acceleration time are the other criteria that have been studied for diagnosis of RAS. Handa et al. (1986) investigated the velocity waveforms of the renal artery and its segmental branches in renal hilum. Using these waveforms they described acceleration index and acceleration time, which they reported to be indicators of an upstream stenosis. Similar indirect changes of a significant proximal stenosis were described by Stavros at the Annual Meeting of the RSNA in 1990. According to our experience, acceleration parameters have relatively low reproducibility. "Early systolic notch," which was also described by Stavros (RSNA 1990) in normal segmental arteries, makes the measurement of acceleration and acceleration time more complicated. Some of these typical waveforms that we observe have a delayed second peak, which has a higher value than the initial one. In this case, it is controversial which one of the peaks should be used to measure acceleration and acceleration time. On the other hand, segmental and interlobar arteries do not always demonstrate "early systolic notch" in normal subjects. These waveforms have an initial slope up to peak, which is generally parabolic instead of being straight. In these cases, it is practically impossible to determine acceleration parameters, especially the "acceleration index" described by Handa et al. (1986). We noticed that intrarenal arterial waveforms dampen downstream to a significant RAS. While intrarenal arterial velocities are dependent on individual variations in systemic hemodynamics and anatomy, we do not think that low velocity values alone can be used as a criterion for RAS. S/D, RI, and PI values ofintrarenal arteries have been studied for the diagnosis of renal parenchymal disease, or to evaluate renal allograft dysfunction (Allen et al. 1988; Patriquin et al. 1989; Platt et al. 1990; Ritkin et al. 1987; Wan et al. 1988). In all these studies, the focus of attention was the upper normal thresholds of these indexes. Now, owing to our results, we suggest that the lower normal limits of these values also deserve the same interest and attention. S/D, RI,
9
and PI values ofintrarenal arteries in the stenotic kidneys were significantly lower than those of other kidneys. The same observation was made by comparing the two halves of the same kidney of a very typical case, where one kidney had a well-perfused lower half but, because of RAS, poorly perfused upper half. Low intrarenal RI values have also been reported in cases of renal AVM. However, this finding is limited to a specific area as other typical Doppler findings of AVM such as high-velocity intrarenal jets and arterialization of the draining veins, since AVM is a local pathological process (Middleton et al. 1989; Takebayashi et al. 1991). In cases of AVM, low resistivity is present in the supplying artery of the lesion, in contrast to the RAS(+) cases in our study where low S/D, RI and PI values were found downstream to the stenosis. The malformation can be clearly located with the help of pulsed-wave or color Doppler aliasing. CDI, in particular, facilitates the depiction of high-velocity intrarenal jets. None of the kidneys in the study was found to have the above mentioned Doppler findings or the angiographic evidence of AVM. The kidney with intrarenal arterial stenosis had a focal area of low-resistivity and high-velocity jets, but low resistivity was limited downstream to the lesion, and the draining vein was not arterialized. The Doppler waveform depends on vascular compliance and the presence of any disease upstream or downstream (Hoskins 1990). RI and PI reflect both distal and proximal hemodynamics (Greene et al. 1987). The waveform changes we observed might be caused by the decrease of vascular resistance in ischemic renal parenchyma and/or the direct physiological effect of stenosis on hemodynamics. The kidneys are capable of autoregulating renal blood flow and glomerular filtration rate within narrow limits. Autoregulatory responses are mediated by active adjustment of smooth muscle tone. The major site for autoregulatory resistance adjustment is preglomerular. At present, there are two hypotheses as potential mechanisms of renal autoregulation. The macula densa hypothesis invokes the tubuloglomeru-
T a b l e 4. C o m p a r i s o n o f S/D, RI a n d PI values before a n d after P T R A in R A S ( + ) patients.
Stenotic kidney Pre-PTRA Post-PTRA Contralateral kidney Pre-PTRA Post-PTRA
S/D
RI
PI
1.77 _+ 0.28 2.61 +_ 0.63
0.42 _+0.10 0.60 _+0.08
0.57 + 0.17 1.00 _+0.26
2.84 + 0.64 2.60 _+ 0.34
0.63 + 0.10 0.61 _+0.05
1.03 + 0.25 1.06 + 0.21
Note: PTRA - Percutaneous Transluminal Renal Angioplasty,
lO
Ultrasound in Medicineand Biology
Volume 19, Number 1, 1993
'r
INDEX VALUE
4
::::::::::::::::::::::::::::::::::::::
.......
PREPTRA
PO8TPTRA 8PI
~
RPI
I
PPI
Fig. 6. Comparison of perfusion indexes before and after PTRA in patients with RAS. lar feedback (TGF) mechanism. It predicts that disturbances that increase tubular fluid flow will elicit vasoconstriction, whereas decreases in flow, as in the example of a significant RAS, will cause vasodilation, mainly in afferent arterioles. The myogenic hypothesis imparts to renal vascular smooth muscle the ability to sense changes in vessel wall tension and to respond with appropriate adjustments in tone. For example, an increase in wall tension, occurring as a passive response to an elevation in arterial pressure, is thought to stimulate a sensor element and initiate a chain of events resulting in vascular smooth muscle contraction. Interlobular and afferent arterioles have been reported to exhibit myogenic responses to change in wall tension (Navar et al. 1989). Schwietzer and Gertz (1979) demonstrated the preglomerular vascular resistance changes in clamped and unclamped kidneys of two-kidney Goldblatt rats by using micropuncture techniques. The preglomerular vascular resistance increased by 51% in unclamped kidneys, and 21% in clamped kidneys compared to that of controls. Although there seems to be a discrepancy about the relative preglomerular vascular resistances of stenotic and normal kidneys between the above mentioned hypotheses and the results by Schwietzer and Gertz (1979), all are in agreement that a reduction in preglomerular vascular resistance exists in stenotic kidney compared to that of the contralateral kidney. This is probably reflected in RI, which has been shown to be a good indicator of renovascular resistance with experimental studies (Norris and Barnes 1984). The same is also true for PI and S/D, which are all directionally similar, although quantitatively different.
When time-varying flow passes through a stenosis, its pulsatility is affected. Resistance ofstenosis and compliance of downstream arteries combine to absorb high-frequency components of the pressure pulse, resulting in a less pulsatile flow downstream from a stenotic lesion (Burns 1988). This is exactly what we observed in the Doppler waveforms of the segmental and interlobar arteries in significantly stenotic kidneys. For all of the perfusion indexes, there was no statistically significant difference between the control and RAS(-) groups, whereas all indexes were higher in the RAS(+) group than those of the other two groups. Since there was not any case of AVM in our series, we could not obtain associated perfusion index values. In cases of renal AVM, perfusion index values could also be expected to be high, as S/D, RI and PI values of the supplying artery would be significantly lower than those of the contralateral kidney. However, AVM could be easily differentiated from RAS with the help of the typical Doppler findings mentioned above. The S/D, RI and PI values of all RAS(+) patients rose to normal values after PTRA. This finding is in accordance with those of Soulen (RSNA 1991). The perfusion indexes also returned to normal lower values after the procedure. We think that low S/D, RI and PI values or asymmetric distribution of these indexes alone cannot be depended on as a criterion of significant RAS, but a combination, such as perfusion indexes, should be used. Low S/D, RI and PI values probably demonstrate an insufficient blood supply, due to significant RAS or to central reasons. The latter was observed in the patient with Takayasu's arteritis, who had a signifi-
Intrarenal Doppler findings of RAS • S. SOREYYAQ)ZBEKel aL
cant aortic stenosis proximal to the renal arteries. Bilateral low indexes with irregular waveforms were very remarkable. Accessory renal arteries were mentioned by other authors as a factor that limits the accuracy of Doppler US in diagnosing RAS (Berland et al. 1990; Desberg et al. 1990; Eidt et al. 1990; Greene et al. 1987; Robertson et al. 1988), Deriving Doppler signals from the parenchymal areas perfused by accessory arteries seems to be easier and more applicable than demonstrating them. For this purpose, it would be better to sample and analyze two or more interlobar arteries from different parts of every kidney instead of one segmental and one interlobar artery, as we did in our study. The index values should then be compared with those obtained from the identical region of the contralateral kidney. The same technique may have a greater chance of revealing a renal artery branch or segmental artery stenosis, which are impossible to detect by scanning the main renal arteries only. As a matter of fact, SPI, RPI, and PPI values of the patient with intrarenal stenosis, obtained by comparing the values of the stenotic upper half of the kidney with those of either the lower half of the kidney with those of either the lower half of the same kidney or contralateral kidney, were all in the pathological range. It is necessary to have carefully controlled prospective studies on the waveform changes we observed, and perfusion indexes we suggested, with a larger number of RAS(+) patients. In fact, we have begun such a new study in our department. However, the results and findings of this preliminary study with a limited number of RAS(+) patients are quite remarkable. Accordingly, we suggest a new method in the diagnosis of RAS with which the factors limiting the routine use of Doppler US, such as tympanites, obesity or long examination duration, may be overcome. In our opinion, in addition to the main renal arteries, renal parenchymal arteries should be examined for the indirect findings of an upstream RAS. SUMMARY In this prospective, double-blind study we evaluated the intrarenal arterial waveforms in the kidneys of normal and hypertensive cases. In both the right and left kidneys of normal and hypertensive cases without a significant renal artery stenosis, the results indicated a symmetric finding in all three S/D, PI and RI ratios. All these index values were significantly lower in the stenotic kidneys than those of the contralateral normal kidneys, the kidneys of hypertensive cases without renovascular disease and control subjects. To
11
quantify this observation we suggest "perfusion indexes," which require more studies on a greater number of hypertensive cases. It was concluded that measuring the index values of intrarenal arterial waveforms is easier and more accessible in diagnosing RAS than obtaining the velocity waveforms of the main renal artery. REFERENCES Allen, K. S.; Jorkasky, D. K.; Arger, P. H.; Velchik, M. G.; Grumbach, K. Renal allografts: Prospective analysis of Doppler sonography. Radiology 169:371-376; 1988. Avasthi, P. S.; Voyles, W. F.; Greene, E. R. Noninvasive diagnosis of renal artery stenosis by echo-Doppler velocimetry. Kidney Int. 25:824-829; 1984. Berland, L. L.; Koslin, D. B.; Routh, W. D.; Keller, F. S. Renal artery stenosis: Prospective evaluation of diagnosis with color duplex US compared with angiography (work in progress). Radiology 174:421-423; 1990. Bums, P. N. Hemodynamics. In: Taylor, K. J. W.; Burns, P. N.; Wells, P. N. T., eds. Clinical applications of Doppler ultrasound. New York: Raven Press; 1988:46-75. Desberg, A. L.; Paushter, D. M.; Lammert, G. K.; Hale, J. C.; Troy, R. B. Renal artery stenosis: Evaluation with color Doppler flow imaging. Radiology 177:749-753; 1990. Dunnick, N. R.; Sfakianakis, G. N. Screening for renovascular hypertension. Radiol. Clin. North Am. 29:497-510; 1991. Eidt, J. F.; Harward, T.; Cook, J. M.; Kahn, M. B.; Troillet, R. Current status of duplex Doppler ultrasound in the examination of the abdominal vasculature. Am. J. Surg. 160:604-609:1990. Franklin, S. S. Renovascular hypertension. In: Massry, S. G.; Glassock, R. J., eds. Textbook of nephrology. 2nd ed. Baltimore: Williams & Wilkins; 1989:1081-1090. Gottlieb, R. H.; Luhmann, K., IV; Pates, R. P. Duplex ultrasound evaluation of normal native kidneys and native kidneys with urinary tract obstruction. J. Ultrasound Med. 8:609-611 ; 1989. Greene, E. R.; Avasthi, P. S.; Hodges, J. W. Noninvasive Doppler assessment of renal artery stenosis and hemodynamics. J. Clin. Ultrasound 15:653-659; 1987. Greene, E. R.; Venters, M. D.; Avasthi, P. S.; Conn, R. L.; Jahnke, R. W. Noninvasive characterization of renal artery blood flow. Kidney Int. 20:523-529:1981. Handa, N.; Fukunaga, R.; Uehara, A.; Etani H.; Yoneda, S. EchoDoppler velocimeter in the diagnosis of hypertensive patients: The renal artery Doppler technique. Ultrasound Med. Biol. 12:945-952: 1986. Hawkins, P. G.; McKnoulty, L. M.; Gordon, R. D.; Klemm, S. A.; Tunny, T. J. Noninvasive renal artery duplex ultrasound and computerized nuclear renography to screen for and follow progress in renal artery stenosis. J. Hypertens. 7 (Suppl. 6):S184S185; 1989. Hoskins, R. Quantitative techniques in arterial Doppler ultrasound. Clin. Phys. Physiol. Meas. 11 (Suppl. A):75-80; 1990. Middleton, W. D.; Kellman, G. M.; Melson, G. L.; Madrazo, B. L. Postbiopsy renal transplant arteriovenous fistulas: Color Doppler US characteristics. Radiology 171:253-257; 1989. Navar, L. G.; Carmines, P. K.; Paul, R. V. Renal circulation. In: Massry, S. G.; Glassock R. J., eds. Textbook of nephrology. 2nd ed. Baltimore: Williams & Wilkins; 1989:43-53. Norris, C. S.; Barnes, R. W. Renal artery flow velocity analysis: A sensitive measure of experimental and clinical renovascular resistance. J. Surg. Res. 36:230-236; 1984. Patriquin, H. B.; O'Reagan, S.; Robitaille, P.; Paltiel, H. Hemolytic-uremic syndrome: lntrarenal arterial Doppler patterns as a useful guide to therapy. Radiology 172:625-628; 1989. Platt, J. F.; Ellis, J. H.; Rubin, J. M.; DiPietro, M. A.; Sedman, A. B.
12
Ultrasound in Medicine and Biology
Intrarenal arterial Doppler sonography in patients with nonobstructive renal disease: Correlation of resistive index with biopsy findings. Am. J. Roentg. 154:1223-1227; 1990. Piatt, J. F.; Rubin, J. M.; Ellis, J. H. Distinction between obstructive and nonobstructive pyelocaliectasis with duplex Doppler sonography. Am. J. Roentg. 153:997-1000; 1989. Rilkin, M. D.; Needleman, L.; Pasto, M. E.; Kurtz, A. B.; Foy, P. M. Evaluation of renal transplant rejection by duplex Doppler examination: Value of the resistive index. Am. J. Roentg. 148:759-762; 1987. Rittgers, S. E.; Norris, C. S.; Barnes, R. W. Detection of renal artery stenosis: Experimental and clinical analysis of velocity waveforms. Ultrasound Med. Biol. 11:523-531; 1985. Robertson, R.; Murphy, A.; Dubbins, P. A. Renal artery stenosis:
Volume 19, Number 1, 1993 The use of duplex ultrasound as a screening technique. Br. J. Radiol. 61:196-201; 1988. Schwietzer, G.; Gertz, K. H. Changes of hemodynamics and glomerular ultrafiltration in renal hypertension of rats. Kidney Int. 15:134-143; 1979. Strandness, D. E. Duplex scanning in diagnosis of renovascular hypertension. Surg. Clin. North Am. 70:109-117; 1990. Takebayashi, S.; Aida, N.; Matsui, K. Arteriovenous malformations of the kidneys: Diagnosis and follow-up with color Doppler sonography in six patients. Am. J. Roentg. 157:991995; 1991. Wan, S. K. H.; Ferguson, C. J.; Cochlin, D. L. L.; Evans, C.; Griffiths, D. F. R. Duplex Doppler ultrasound in the diagnosis of acute renal allografi rejection. Clin. Radiol. 40:573-576; 1988.