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Historical Background
As early as in 1836, Richard Bright reported the first potential association between
hypertension and renal disease when he associated autopsy findings of kidney
disease and cardiac hypertrophy to an increased peripheral resistance . 7
In 1898 Tigerstedt and Bergman discovered that extract from the renal cortex of
rabbits caused a marked increase in AP when injected intravenously (i.v.) to
normotensive rabbits 8. They hypothesized that the renal cortical tissue extract
contained a hypertensive factor and hence named it renin 8. The first successful
experimental model of arterial hypertension caused by manipulation of the kidney
was developed in 1934 when Goldblatt et al. showed that clamping of renal arteries
in dogs produced a reproducible and persistent rise in AP. 9 Clamping other large
arteries as splenic or femoral arteries had no effect on AP, indicating that
hypertension resulted specifically from renal ischemia caused by renal artery
stenosis (RAS) 4. In 1938, Leadbetter and Burkland reported the first successful
treatment of hypertension by nephrectomy in a patient with RAS 9. Treatment of
RAS changed with the introduction of surgical revascularization in 1954 6 and
later on, in 1978, with the introduction of percutaneous transluminal renal
angioplasty (PTRA)9.
3.6.Screening Tests
Duplex Ultrasonography will be discussed later.
3.6.1.Magnetic Resonance Angiography
Magnetic resonance angiography (MRA) visualizes the main renal arteries without
use of a radiocontrast agent or exposure to radiation. Its usefulness extends to
persons with renal insufficiency or those with a history of radiocontrast allergy.
Also, it is a reasonable choice for persons with a high likelihood of the disorder
who have concomitant severe, diffuse atherosclerosis and, thus, are at high risk of
atheroembolization with angiography. Field limitations may decrease the ability to
see lesions in the distal main renal arteries or lesions in branch vessels (common
sites of fibromuscular disease). Accessory renal arteries may not be identified, the
degree of arterial stenosis may be overestimated, and persons prone to
claustrophobia may not tolerate being placed in the magnetic resonance equipment.
Renal stents cause imaging artifacts, and persons with cardiac pacemakers,
metallic artificial cardiac valves, or cerebral artery aneurysm clips cannot be
imaged. Sensitivity is 80% to 90% (less for fibromuscular dysplasia), and
specificity is 90%. This is an expensive screening test.1
3.6.2.Spiral Computed Tomographic Angiography
Spiral CT angiography offers excellent three-dimensional images but requires a
considerable amount of radiocontrast agent and patient cooperation. This is an
option for persons with normal renal function who do not have a contrast allergy
and in whom MRA is contraindicated. Renal stents do not cause imaging artifacts.
Sensitivity and specificity are similar to those for MRA. This is also an expensive
test. Other noninvasive tests are available to screen for renal artery stenosis;
however, they are used less often because the test characteristics are inferior
compared with those of duplex ultrasonography, MRA, and spiral CT angiography.
Historically, the intravenous pyelogram (IVP) was the mainstay screening
test for renovascular hypertension. For screening, radiographs that are taken at 1minute intervals for the first 5 minutes after injection of contrast medium are used
to identify a delay in the appearance of contrast medium in the renal collecting
system on the side of a renal artery stenosis. This is referred to as the hypertensive
IVP. Characteristic findings on a hypertensive IVP suggesting renal artery stenosis
are 1) unilateral reduction in renal size (1.5-cm decrease in pole-to-pole diameter
of the smaller kidney); 2) delayed appearance of contrast medium in the collecting
system of the ischemic kidney; 3) hyperconcentration of contrast medium in the
per hour or 400% or more if the baseline PRA is less than 3 ng/mL per hour. The
results are compromised if the person has renal insufficiency. Sensitivity is 39% to
100%, and specificity is 72% to 100%. Because the results can be influenced by
many factors that are difficult to identify and control, predictive accuracy is low.1
3.6.5.Renal Vein Renins
Lateralization of renal vein renins is a good predictor of a favorable outcome after
intervention for unilateral renal artery stenosis; however, because many factors that
influence renin secretion are difficult to identify and control (as noted for the
captopril test), the predictive value of the test is low. It is invasive and expensive.
Lateralization is present if the ratio of renin activity on the affected side compared
with that on the normal side is 1.5:1.0 or more. Sensitivity is 63% to 77%, and
specificity is 60% to 95%.1
3.6.6.Digital Venous Subtraction Angiography
Digital venous subtraction angiography uses contrast media, but access to the
circulation is through a peripheral vein. With the advent of newer screening tests, it
is used less often. This technique provides adequate visualization of the proximal
portion of the main renal arteries (usual location of atherosclerotic disease) in 90%
of persons but less effective visualization of the distal portions of the main renal
arteries or branches (the usual location of fibromuscular dysplasia). This technique
is expensive, and in 20% to 30% of persons, neither renal artery is identified
because of superimposition of abdominal vessels or patient motion. Both the
sensitivity and the specificity are 85% to 90%.1
3.6.7.Renal Arteriography
Conventional renal arteriography is the diagnostic standard test to identify renal
artery stenosis. In clinical situations in which the pretest likelihood is high (50%),
a negative result from a screening test still leaves a significant posttest probability
of disease (20%). Thus, in these settings, consideration should be given to
performing renal angiography without first performing screening tests. Exceptions
may be when patients have diabetes or severe generalized atherosclerosis with
concomitant renal insufficiency and use of a noninvasive test initially, such as
MRA or duplex ultrasonography, may be reasonable. This is because in these
settings, the risk of contrastinduced acute renal failure or atheroembolism is
significant. Contrast toxicity from angiography can be reduced with the use of
gadolinium or carbon dioxide as the contrast agent. However, these techniques do
not reduce the risk of atheroembolism.1
3.8.1.Examination Technique
One way of identifying the renal arteries at their origins just below the easily
visualized superior mesenteric artery is to localize the latter in transverse
orientation and to then move the transducer 12 cm downward and look for the
renal arteries as they arise from the aorta to the left and right . A second landmark
is the left renal vein (hypoechoic, broader band) which overcrosses the aorta before
opening into the vena cava and along its route passes between the superior
mesenteric artery and the aorta. The left renal artery typically arises some
millimeters below the right renal artery and both do not usually take a strictly
horizontalcourse but move slightly downward. The right renal artery first courses
anteriorly in a slightly curved fashion and then arches underneath the vena cava.
The origins as well as the first 3 cm of the renal arteries can be visualized and
evaluated in over 90% of cases while visualization of the middle third is often
incomplete due to overlying bowel gas, especially on the left. The middle segment
of the renal artery is easier to scan on the right where the vena cava can serve as an
acoustic window. Interfering bowel gas can be displaced by pressing the transducer
against the bowel until the vessel is seen. The transducer is then moved to the right
or left to achieve an optimal angle for sampling of the Doppler spectrum. The
distal third can be scanned continuously from the flank starting at the renal hilum
and following the course of the vessel proximally . From this transducer position, it
is also possible to continuously record an adequate Doppler spectrum with a
relatively small angle. The individual segmental arteries are identified in the color
flow mode and evaluated for stenoses at their origins during shallow breathing or
breath-holding. If renal artery infarction is suspected, the renal parenchyma is
evaluated for perfusion defects that are seen on color duplex scans as wedgeshaped areas without color coding (high but artifact-free gain, low pulse repetition
frequency).2
3.8.2.Normal Findings
Supplying a low-resistance parenchymal organ, the renal arteries have a flow
profile with little pulsatility and a large diastolic component. Measurements
performed in 102 renal arteries without abnormalities on control angiography
yielded a mean peak systolic velocity of 84.7 13.9 cm/s and an end-diastolic
velocity of 31.2 7.8 cm/s. The Pourcelot index was 0.66 0.07 (findings by our
group, 1988). Visualization of the renal arteries for exclusion of a stenosis by
duplex scanning is possible in 8590% of cases; the proximal third as the preferred
site of atherosclerotic stenoses can be evaluated in over 90%of cases. The flow
velocities reported in the literature vary widely from one study to the next but also
within the studies. The range is 60140 cm/s for peak systolic velocity and 2065
cm/s for end-diastolic velocity with a Pourcelot index of 0.60.8. Reported
diameters range from 58 mmThe peak systolic and diastolic velocities and the
Pourcelot index are affected by vessel elasticity and peripheral resistance.
Moreover, they are influenced by systemic blood pressure. In diabetics, medial
sclerosis with decreased wall elasticity and parenchymal changes result in a
decreased diastolic flow and a higher Pourcelot index. Peak systolic velocity is
slightly higher than in subjects with normal vessels. 2
3.8.3.Doppler Interpretation
There are many proposed guidelines for Doppler interpretation. Proposed
parameters to assess for stenosis include the peak systolic velocity (PSV), renal
aortic ratio (RAR; defined as highest systolic velocity in renal artery divided by
aortic systolic velocity, with aortic velocity measured at or above SMA origin),
acceleration time, acceleration index, renal interlobar ratio, and renal-renal
ratio. The Cleveland Clinic used a combination of RAR of 3.5 or greater or PSV
of 200 or greater as the criterion for renal artery stenosis of more than 60%. We
use a variation of the Cleveland Clinic guidelines, using the same RAR as the
study but a higher PSV. We have done internal validation of our guidelines but
continue to look for ways to improve them. False-Positive/False-Negative
Results. To obtain the highest accuracy, it is important to avoid relying solely on
the numerical data obtained. When a high velocity is seen or when the renal aortic
ratio is high, the interpreting radiologist must also actively look for secondary
signs of stenosis, such as a characteristic harsh audible signal at the site of stenosis,
increased diastolic flow, color bruit, and post-stenotic turbulence. Without
ancillary findings, the interpreter must consider the possibility that the high
velocity or high RAR represents a false-positive result. False-negative findings are
most a risk when visualization is marginal and the entire artery has not been
adequately evaluated. In perhaps 5% to 10% of patients, accurate diagnosis cannot
be made because of inadequate visualization of one or both arteries. Attention to
intrarenal waveforms is also of some importance. A highly abnormal waveform
can be a valuable indicator of stenosis. A delayed systolic peak (tardus, i.e.,
tardy) and velocities that are greatly decreased (parvus, i.e., puny) can be a
strong sign of a more proximal stenosis. The intrarenal waveform can be analyzed
quantitatively by calculating the systolic rise time and the acceleration . Although
we calculate these parameters, a qualitative assessment of the appearance of the
waveform usually serves just as well. We only rely on a tardus-parvus waveform
to make the diagnosis when the finding is pronounced. An acceleration time
greater than 0.07 second and a slope of systolic upstroke less than 3 m/s2 are
suggested as thresholds to assess for renal artery stenosis. Simple recognition of
the change in pattern may be adequate. Pharmacologic manipulation with captopril
may enhance the waveform abnormalities in patients with renal artery stenosis.
Doppler sonography remains a controversial technique for the detection of native
renal artery stenosis. The use of intravascular contrast agents increases the
technical success rate for the evaluation of renal artery stenosis. It may also play a
role in the assessment and follow-up of patients undergoing renal artery
angioplasty and stent placement.6
The examination is challenging to the uninitiated operator, but establishment of a
renal artery duplex Doppler program can be rewarding. Because of the lower cost
versus other diagnostic tests, Doppler ultrasound lowers the threshold for the
diagnosis of renovascular hypertension. Hurdles mainly relate to the learning curve
and the initial investment of time. Starting a program is more feasible in a large
center where demand will likely be higher than in a smaller facility. Once the
program is mature, the study is financially viable and can result in improved
patient care .6