Alzaiem Al-Azhari University
Faculty of Graduate Studies and Scientific Research
Estimation of the Frequency of Renal Artery Stenosis Among
Hypertensive Patients Using Duplex Sonography in Khartoum in
2014
A Thesis Submitted For Partial Fulfillment of the Requirement of
M.Sc Degree in Medical Diagnostic Ultrasound
Presented By : Dr. Walaa Ismail Musa
Supervisor : Dr. Suzan Omar Abd-AllaMBBS ( Medicine ), M.Sc
(Medical Diagnostic Ultrasound AAU ), MD ( Diagnostic Radiology
SMSB )
2014
XII
(49)
DedicationTo my parents who taught me to help...To my teachers
who made me to know...To my wonderful friends...
AcknowledgementA number of people provided comments, help and
moral support,Special thanks to my supervisor...Dr Suzan Omar
Abd-Alla
Abstract Renal artery stenosis (RAS) is a progressive disease
with many associated morbidities including but not limited to
progressive renal insufficiency, hypertension, myocardial
infarctions, congestive heart failure, stroke, and death. Early
diagnosis of renal artery stenosis is an important clinical
objective because interventional therapy may improve or cure
hypertension, preserve renal function, and prevent development of
end-stage renal failure. The aim of this study is to estimate the
frequency of renal artery stenosis among hypertensive patients in
Khartoum using duplex sonography, and to evaluate the relation
between renal artery stenosis and age, gender, and other co
morbidities of the patient. This study was carried out in Soba
University Hospital, Sharq El-Niel, Khartoum North, and Umdorman
Military Hospital, where 100 hypertensive patients were collected
randomly from different ages and different gender, this study has
been carried out in 7 months.Duplex ultrasound examination was done
on both renal arteries. Frequency of renal artery stenosis is 2%
among studied cases. , the two affected cases are males, in the age
group of 20-40 years, with newly discovered hypertention, and no
associated comorbiditiy, no other kidney sonographic abnormality,
one of them has normal renal function test and the other has
abnormal test. The study emphasized the role of duplex sonography
as a screening and diagnosis tool for renal artery stenosis and the
importance of early scanning. It recommends to improve the local
practice of renal artery duplex by following the universal
protocols and continuous training and machines quality
assurance.
(RAS) . . . 100 7 . 2 20-40 . . .NoContentsPage No
1I
2DedicationII
3AcknowledgementsIII
4Abstract(English)IV
5Abstract (Arabic)V
6Table of contentsVI
7List of abbreviationsVII
8List of tablesIX
9List of figuresXI
Chapter One
1-1Introduction1
1-2Objectives4
Chapter Two
2-1Historical Background4
2-2Renal Circulation Anatomy & Physiology5
2-3Etiology of Renal Artery Stenosis8
2-4Pathophysiology of Renovascular Hypertension9
2-5Clinical Clues of Renovascular Hypertension10
2-6Screening Tests11
2-7Therapy of Renovascular Hypertension17
2-8Duplex Ultrasound of the Renal Artery19
2-9Background Comparative studies25
Chapter Three
3Material &Methodology27
Chapter four
4Results30
Chapter Five
5-1Discussion56
5-2Conclusion58
5-3Recommendations59
References60
Appendix62
AbbreviationsACE angiotensin converting enzyme ACEI angiotensin
converting enzyme inhibitorARB angiotensin receptor blockerAP
arterial pressureCT computed tomographyDPTA
diethylenatriaminepentacetic acidDSA digital substraction
angiographyEDV end diastolic velocityESRD end stage renal
failureFMD fibromuscular dysplasiaIVP intravenous pyelographyMAG3
mercaptoacetyltriglycerinMIP maximum intensity projectionMRA
magnetic resonance angiographyOM outer medullaPRA plasma rennin
averagePTRA percutaneous transluminal renal angioplastyPO2 partial
oxygen pressurePSV peak systolic velocityRAS renal artery
stenosisRAR renoaortic ratioRI resistive indexT99m technetium 99
metastableWHO world health organization
List of TablesTableNamePage No
2-1 Causes of increased RI in renal arteries24
2-2Different sonographic criteria used for diagnosing
renalartery stenosis24
4-1Frequency of Renal Artery Stenosis32
4-2Frequency distribution of patients according to age33
4-3Frequency distribution of patients according to gender34
4-4Frequency distribution of patients according to
occupation35
4-5Frequency distribution of patients according to HTN
duration36
4-6Frequency distribution of patients according to comorbidities
37
4-7Frequency distribution of patients according to RFTs38
4-8 statistics of doppler values and kidney lengths49
4-9Frequency distribution of patients according to spectral
waveform44
4-10Frequency distribution of patients according to other
sonographic abnormalities45
4-11age * Renal artery stenosis Cross tabulation46
4-12gender * Renal artery stenosis Crosstabulation47
4-13HTN duration * Renal artery stenosis Crosstabulation48
4-14co mrbidities * Renal artery stenosis Crosstabulation49
4-15RFTs * Renal artery stenosis Crosstabulation50
4-16other sonographic abnormalities * Renal artery stenosis
Crosstabulation51
4-17HTN duration* Rt renal artery RI Crosstabulation52
4-18HTN duration*Lt renal artery RI Crosstabulation53
4-19RFTs*Rt renal artery RI Crosstabulation54
4-20RFTs *Lt renal artery RI Crosstabulation55
List of FiguresFigure NamePage No
2-1Normal vascular anatomy of the kidney6
2-2CTA MIP image, displaying normal Right and Left Renal
arteries12
2-3DSA showing RAS due to fibromuscular dysplasia16
2-4Renal artery stenosis21
4-1Frequency of Renal Artery Stenosis32
4-2Frequency distribution of patients according to age33
4-3Frequency distribution of patients according to gender34
4-4Frequency distribution of patients according to
occupation35
4-5Frequency distribution of patients according to HTN
duration36
4-6Frequency distribution of patients according to
comorbidities37
4-7Frequency distribution of patients according to RFTs38
4-8Frequency distribution of patients according to Rt kidney
length40
4-9Frequency distribution of patients according to Lt kidney
length40
4-10Frequency distribution of patients according to Rt kidney
PSV41
4-11Frequency distribution of patients according to Lt kidney
PSV41
4-12Frequency distribution of patients according to Rt kidney
RI42
4-13Frequency distribution of patients according to Lt kidney
RI42
4-14Frequency distribution of patients according to Rt kidney
R/A ratio43
4-15Frequency distribution of patients according toLt kidney R/A
ratio43
4-16Frequency distribution of patients according to spectral
waveform44
4-17Frequency distribution of patients according to other
sonographic abnormalities45
4-18age * Renal artery stenosis Cross tabulation46
4-19gender * Renal artery stenosis Crosstabulation47
4-20HTN duration * Renal artery stenosis Crosstabulation48
4-21co mrbidities * Renal artery stenosis Crosstabulation49
4-22RFTs * Renal artery stenosis Crosstabulation
50
4-23other sonographic abnormalities * Renal artery stenosis
Crosstabulation51
4-24HTN duration* Rt renal artery RI Crosstabulation52
4-25HTN duration*Lt renal artery RI Crosstabulation53
4-26RFTs*Rt renal artery RI Crosstabulation54
4-27RFTs*Lt renal artery RI Crosstabulation55
Chapter One Introduction
Chapter One1.1. Introduction1.1.1. definitions High blood
pressure (hypertension) is a major factor in the pathogenesis of
coronary heart disease, stroke and renal failure . The World Health
Organization has defined hypertension as a systolic blood pressure
of 140 mmHg or greater and/or a diastolic blood pressure of 90 mmHg
or greater in subjects who are not receiving antihypertensive
medication. Hypertension is further stratified into two categories,
essential and secondary hypertension. Known secondary forms of
hypertension account for approximately 10% of all cases of
hypertension. Secondary forms are often considered in patients who
have clinical features that are inconsistent with essential
hypertension. Common general clinical clues are an unusual age at
onset (younger or older than for essential hypertension), a sudden,
unexplained increase in blood pressure from a previous state of
control, or primary or acquired resistance to treatment. Secondary
causes include drugs, increasing obesity, and obstructive sleep
apnea. The clinical clues suggestive of secondary hypertension
should be recognized, and when secondary hypertension is suspected,
consultation with a subspecialist should be considered.(1)
Renovascular hypertension is the most common form of potentially
curable secondary hypertension. It occurs in 1% to 3% of the
general hypertensive population, in 10% of persons with resistant
hypertension, and in up to 30% of those with hypertensive crisis.
It is less common in African Americans than in Caucasians.(1) Renal
artery stenosis is commonly caused by either fibromuscular
dysplasia or atherosclerosis. Atherosclerotic stenosis virtually
always occur at the origins of the renal arteries from the aorta
or, very rarely, at the branching into segmental arteries. They
predominantly affect older males with other obstructive vascular
diseases. In contrast fibromuscular stenosis nearly exclusively
involves the middle thirds of the renal arteries and primarily
occurs in young women. Hence, selective duplex scanning of the
respective renal artery segment according to the suspected cause of
stenosis can be performed.(2)1.1.2. Screening Tests Although
several tests are available to screen for renal artery stenosis,
duplex renal ultrasonography, magnetic resonance angiography, and
spiral computed tomographic (CT) angiography are considered the
initial screening tests of choice.(1) Duplex ultrasonography is
noninvasive and does not use contrast media. Its usefulness extends
to persons who have renal insufficiency or a history of contrast
allergy. Performance of the test does not require discontinuation
of any antihypertensive drug. It is of low cost, widely available,
relatively easy to perform, requires minimal patient preparation,
and does not use ionizing radiation . It identifies increases in
blood flow velocity that occur with luminal narrowing of a renal
artery. (1) Criteria for a positive test are 1) a ratio of peak
flow velocity in the involved renal artery to peak flow velocity in
the aortaof more than 3.5 and 2) renal artery peak systolic flow of
180 cm/s or more.(1)1.1.3. importance of the study According to
world health statistic published by WHO in 2013, the prevalence of
raised blood pressure in Sudan in 2011 was 40% . (3) This
represents a considerable rise from 7.5% in 1985 through 18.2% in
2002. (4) A study about renal replacement therapy in Sudan revealed
that hypertension was the most commonly reported cause of ESRD
(26.1%).The diagnosis of hypertensive nephrosclerosis is difficult
to ascertain even in patients with long standing hypertension. Such
patients may have had secondary hypertension due to undiagnosed
kidney disease.(5) Early literature indicated the potential of
doppler for improving the sonographic assessment of renal
dysfunction. Changes in intrarenal spectra (quantified using RI)
were associated with acute or chronic urinary obstruction, several
intrinsic native renal diseases, renal transplant rejection, and
renal vascular disease. . A review indicated that most physicians
do not refer these patients for doppler study, which may have been
caused by a lack of understanding of the hemodynamic changes that
influence doppler spectra.(6)
1.2.Objectives1.2.1. General Objective To estimate the frequency
of renal artery stenosis among hypertensive patients in Khartoum
using duplex sonography .1.2.2. Specific Objectives1. To evaluate
the relation between renal artery stenosis and age, gender, and
other co morbidities of the patient2. . To explore other kidney
sonographic abnormalities that may associate renal artery
stenosis.3. To evaluate the relation of measurable doppler values
with the duration of hypertension, and renal function in
hypertensive patients.
Chapter TwoLiterature Review & Background Studies
Chapter Two
2. Literature Review
2.1.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 arterial pressure
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. 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).
Figure 2.1 : Normal vascular anatomy of the kidney(9)2.2.Renal
Circulation Anatomy and Physiology The kidneys play an essential
role in maintaining a stable internal milieu for optimal cellular
function (homeostasis) through the excretion of metabolic waste
products and adjustment of urinary excretion of water and
electrolytes. To achieve this homeostatic function, a high
proportion of cardiac output (20-25%) passes through the renal
circulation producing about 180 liters of glomerular filtrate
(primary urine) per day. In the tubular system the reabsorption of
water and electrolytes is adjusted to match the prevailing needs
while waste products are retained in the urine and excreted. Almost
all ( 99%) of the filtered water and sodium is normally reabsorbed
in the tubules .(10,11) The kidneys receive their blood supply from
the main renal arteries which arise from the abdominal aorta.
Before reaching the hilum of the kidney, the renal artery generally
divides into anterior and posterior branches which in turn give
rise to four or five segmental arteries. The segmental arteries
divide into interlobar arteries, which progress towards the cortex.
At the junction between the cortex and medulla, interlobar arteries
change course and become arcuate arteries that run in parallel to
the kidney surface. These, in turn, give rise to interlobular
arteries which radiate into the cortex and divide into afferent
arterioles supplying blood to the glomeruli. Each afferent
arteriole supplies blood to a glomerulus, a tuft of capillaries
attached to the mesangium and enclosed in Bowmans capsule.
Glomeruli are drained by efferent arterioles that in the cortex
give rise to the peritubular capillary plexus . Efferent arterioles
from juxtamedullary glomeruli form vasa recta capillaries that form
long hair-pin loops that turn in the medulla . Thus, the renal
circulation consists of two capillary beds connected in series by
the efferent arteriole. The first in the series is the glomerular
capillary bed which is the site of filtration and formation of
primary urine and the second is the peritubular capillary bed which
transports reabsorbed water and solutes back to the systemic
circulation. Total renal blood flow (RBF) in a healthy adult is
approximately 1.2 L/min which corresponds to about 20-25% of
cardiac output. The high RBF is required to maintain a high GFR and
effective excretion of waste products. Consequently, oxygen
delivery to the kidneys is very high and renal oxygen extraction
low. However, there is a marked regional difference in blood flow
distribution in the kidney . About 90% of total RBF is distributed
to the cortex where the partial pressure of oxygen (pO2) is high (
50 mmHg), whereas approximately 10% of RBF goes to the medulla
where the pO2 is low ( 10-20 mmHg). In addition, oxygen consumption
in the outer medulla (OM) is high due to active transport of sodium
in the thick ascending loop of Henle making the OM vulnerable to
ischemic injury . However, low local blood flow in the medulla also
plays important physiological roles in preventing washout of the
medullary hyperosmotic gradient which is necessary for effective
water reabsorption and urine concentration. (10,11)2.3.Etiology of
renal artery stenosis RAS can be caused by a variety of lesions. In
Western populations atherosclerosis and fibromuscular dysplasia
(FMD) are the main two causes of RAS. Atherosclerosis accounts for
about 90% of all cases of RAS. These lesions are commonly ostial
and are in many cases extensions of atheromatous aortic plaques
that involve the proximal 1-2 cm of the renal artery 23, 24.
Patients with ARAS are typically over the age of 50 years and males
are more commonly affected than females. ARAS is usually a
manifestation of generalized atherosclerosis and hence these
patients frequently have coronary artery disease (about 20 %) and
peripheral vascular disease (about 35 %) 23, 24. FMD accounts for
about 10% of all cases of RAS. Medial fibroplasia is the most
common subtype of FMD (7580%) . The right renal artery is more
commonly affected and the disease is most prevalent in 25- to 50-
year old females . (12,13) FMD may involve other major arteries,
commonly internal carotid arteries, and less often the vertebral,
iliac, subclavian, visceral and coronary arteries. The etiology of
FMD is unknown although a number of factors have been suggested,
including: a) genetic predisposition. b) hormonal influence, in
view of the predominance in females. c) mechanical factors, such as
stretching and trauma to the blood vessel wall, and d) ischemia of
the vascular wall due to fibrotic occlusion of the vasa
vasorum,(1)
2.4. Pathophysiology of Renovascular Hypertension Critical
stenosis of a renal artery (i.e., 70% luminal narrowing) increases
renin production from the ischemic kidney. Renin acts on
circulating renin substrate to produce angiotensin I, which is
converted to angiotensin II (a potent vasoconstrictor) by ACE in
the lung and other tissues. In addition to vasoconstriction,
angiotensin II directly increases renal sodium reabsorption and
also stimulates aldosterone production, resulting in extracellular
volume expansion. Angiotensin II also stimulates the sympathetic
nervous system, contributing further to increased vascular
resistance, and stimulates thirst and the release of vasopressin,
contributing further to increased extracellular volume. In
unilateral disease, the nonischemic kidney is subjected to
increased perfusion, resulting in higher sodium excretion and
suppression of renin release. These effects lessen the degree of
hypertension but perpetuate underperfusion of the ischemic kidney,
which, in turn, perpetuates excess renin production. In bilateral
disease, initial increases in renin cause extracellular volume
expansion and volume-dependent hypertension, which persists because
there is no contralateral normal kidney to excrete more sodium. In
persons with bilateral disease, the hypertension is volume
dependent but becomes renin dependent with extracellular volume
depletion. Correcting renal ischemia eliminates the stimulus for
excess rennin release and can cure or lessen hypertension. In
unilateral renal artery stenosis, prolonged hypertension eventually
causes nephrosclerosis in the nonischemic kidney (in combination
with other cardiovascular risk factors) or ischemic injury to the
involved kidney. If either occurs, relieving renal arterial
stenosis may not cure hypertension. The longer the duration of
hypertension before diagnosis, the greater the likelihood of these
untoward renal outcomes and the less the likelihood of cure of
hypertension with intervention.(1)2.5.Clinical Clues of
Renovascular Hypertension Clues suggesting renovascular
hypertension include lack of a family history of hypertension,
onset of hypertension before age 30 (consider fibromuscular
dysplasia, especially in a woman), onset of hypertension after age
50 (consider atherosclerotic renovascular disease, especially in a
smoker or a person with coronary or peripheral arterial disease),
presentation with accelerated or malignant hypertension, or sudden
worsening of preexisting hypertension in a middle-aged or older
person (renovascular hypertension superimposed on essential
hypertension). Persons with cardiovascular risk factors (tobacco
use, hyperlipidemia, or diabetes) are at increased risk of
atherosclerotic renal artery stenosis. The most important physical
finding is an abdominal bruit, especially a high-pitched
systolic-diastolic bruit in the upper abdomen or flank. However,
50% of persons with renovascular hypertension do not have this
finding. Other physical clues are severe retinopathy of accelerated
or malignant hypertension (hemorrhages, exudates, and papilledema)
or evidence of atherosclerotic occlusive disease in other vascular
beds (atherosclerotic renal artery stenosis of >50% is observed
in up to 20% of persons with coronary artery disease and in up to
50% of persons with peripheral arterial disease). Laboratory
abnormalities are hypokalemia (due to secondary aldosteronism), an
increased serum level of creatinine, proteinuria (rarely in the
nephrotic range), and a small kidney seen on an imaging study.
Underlying bilateral renal artery stenosis may be indicated by an
acute decline in renal function (20% increase in serum creatinine)
either after the initiation of therapy with an ACEI or an ARB or
after a drug-induced, sudden decrease in blood pressure. Other
signs in patients presenting with bilateral renal artery stenosis
(i.e., ischemic nephropathy) include the sudden development of
pulmonary edema accompanied by severe hypertension (flash pulmonary
edema), frequent episodes of symptomatic congestive heart failure
accompanied by increases in blood pressure, or a subacute decline
in renal function with or without worsening hypertension. Patients
with atheroembolic renal disease may also present with a sudden
onset or worsening of hypertension and a subacute decline in renal
function. Historical clues (e.g., occurrence after angiography or
vascular surgery), physical findings (distal livedo reticularis and
peripheral emboli), and laboratory abnormalities (increased
erythrocyte sedimentation rate, anemia, hematuria, eosinophilia,
and eosinophiluria) help identify this disorder. In young persons
who have hypertension (even if not severe) of short duration and
suggestive clinical features, evaluation for renovascular disease
is indicated. Renal artery stenosis in these persons can be
identified and corrected with a low risk of morbidity and mortality
and a high probability of cure. Older persons should be evaluated
for renovascular hypertension on a selective basis. In general,
selection should be restricted to persons who have suggestive
clinical features and blood pressure that cannot be controlled
medically or who have an unexplained, observed decline in renal
function or a cardiorenal syndrome (recurrent flash pulmonary edema
or resistant heart failure) and who are considered reasonable risks
for (and are willing to undergo) interventional
therapy.(1)2.6.Screening TestsDuplex Ultrasonography will be
discussed later.2.6.1.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
Fig 2.2: CTA MIP image, displaying normal Right and Left Renal
arteries.(2)
2.6.2.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.(1)
Historically, the intravenous pyelogram (IVP) was the mainstay
screening test for renovascular hypertension. For screening,
radiographs that are taken at 1-minute 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 ischemic kidney; 4) ureteral scalloping by
collateral vessels; and 5) cortical thinning or irregularity.
Sensitivity is 70% to 75%, and specificity is
85%.(1)2.6.3.Captopril Radionuclide Renal Scan Some still consider
the captopril radionuclide renal scan to be a useful screening
test. However, recent reviews suggest a lower test sensitivity than
was reported earlier. Currently, sensitivity is estimated at 75%
and specificity at 85%. Pretest treatment of patients with
captopril (25-50 mg given 1 hour before isotope injection)
increases the sensitivity of the scan compared with that of
standard renography. The rationale is that glomerular filtration in
an ischemic kidney depends on the vasoconstricting effect of
angiotensin II on the efferent arteriole of the nephron to maintain
effective transglomerular filtration pressure. Treatment with an
ACEI causes efferent arteriolar dilatation, with loss of filtration
pressure in the nephron. This causes a decline of glomerular
filtration in the ischemic kidney, with less of an effect on renal
blood flow. These changes are identified with the scanning
technique. The radionuclides used most commonly are iodine 131
orthoiodohippuric acid (OIH) and Tc-99m mercaptoacetyltriglycine
(MAG3), which are markers for renal blood flow (they are excreted
primarily by renal tubular secretion), and Tc-99m
diethylenetriamine pentaacetic acid (DPTA), which is a marker for
glomerular filtration rate (it is excreted primarily by glomerular
filtration). Criteria for a positive test with DPTA are time to
peak activity in the kidney of 11 minutes or more and a ratio of
the glomerular filtration rate between the kidneys of 1.5 or more.
The criterion for a positive test with OIH or MAG3 is residual
cortical activity at 20 minutes of 30% or more of peak activity.
The renal scan is safe for persons with a history of contrast
allergy. The interpretive value is reduced by renal insufficiency
(creatinine >2.0 mg/dL) or by bilateral or branch renal artery
disease. Urinary outflow obstruction may mimic renal artery
stenosis..(1)2.6.4.Captopril Test Acute blockade of angiotensin II
formation by ACEIs induces a reactive increase in PRA. The
magnitude of this increase is usually greater in renovascular
hypertension than in essential hypertension and is the basis for
the captopril test. The use of antihypertensive drugs that
influence the renin-angiotensin-aldosterone axis must be
discontinued for several days before the test. PRA is measured at
baseline and at 60 minutes after administering captopril orally.
Criteria for a positive test are 1) PRA of more than 12 ng/mL per
hour after administration of captopril, 2) absolute increase in PRA
over baseline of at least 10 ng/mL per hour, and 3) increase in PRA
of 150% or more if the baseline PRA is more than 3 ng/mL 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)2.6.5.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)
2.6.6.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)
Figure 2.3 : DSA showing RAS due to fibromuscular
dysplasia.(6)
2.6.7.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 maybe 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)2.7.Therapy for Renovascular Hypertension
Options for the management of renovascular hypertension include
medical and interventional therapies. Percutaneous balloon
angioplasty, stent placement, and surgical procedures to relieve
renal ischemia are the interventional treatments. Goals of
interventional therapy are to cure or improve hypertension or to
preserve renal function. Medical therapy is reserved for persons
who are not considered candidates for interventional therapy
(because of the extent or location of the vascular lesions, high
surgical risk, or uncertainty about the causative significance of
the lesion) or who are unwilling to undergo interventional therapy.
As noted earlier, selection of persons for screening excludes older
persons with controlled hypertension and no evidence of progressive
renal dysfunction even if renovascular disease is suspected.
Percutaneous transluminal angioplasty is the treatment of choice
for amenable lesions caused by fibromuscular dysplasia and is an
option with or without stent placement in some cases of
atherosclerotic renovascular disease. Hypertension is cured in 50%
and improved in 35% of persons with fibromuscular dysplasia. The
failure rate is 15%. In contrast, hypertension is cured in 20% and
improved in 50%, with a failure rate of 30%, in persons with
atherosclerotic renovascular disease. Complications of angioplasty
include groin hematoma, dye-induced azotemia, dissection of the
renal artery, renal infarction, and, rarely, rupture of the renal
artery, with the potential for loss of the kidney and the need for
immediate surgery. Atheroembolization is a risk in older persons
with diffuse atherosclerosis . Stent-supported angioplasty is an
appropriate option for some persons with atherosclerotic renal
artery stenosis, especially for orificial disease. In the presence
of aneurysmal or severe atherosclerotic diseaseof the aorta
requiring concomitant aortic reconstruction, or in persons in whom
percutaneous intervention has failed, surgical intervention is the
treatment of choice. Kidneys with a pole-to-pole length of 8 cm or
less should be removednot revascularizedif intervention is
indicated and removal will not jeopardize overall renal function.
The role of interventional therapy for preservation of renal
function in ischemic nephropathy is uncertain. In most cases, the
underlying disease is atherosclerosis. Improvement in renal
function, defined as a decrease in serum creatinine, occurs in 30%
of cases. In approximately 50% of cases, the creatinine level does
not decrease; however, benefit may be defined as stabilization of
renal function. Of concern is that in 20% of cases, renal function
deteriorates rapidly after the intervention, most likely from a
combination of several factors, including contrast toxicity, acute
renal artery thrombosis, or atheroembolization. The medical
treatment of renovascular hypertension is not different from that
of essential hypertension. Both volume retention (due to
aldosterone) and vasoconstriction (due to activation of the
sympathetic nervous system and angiotensin II) contribute to the
elevation of blood pressure. ACEIs and ARBs can precipitate acute
renal failure in the presence of bilateral renal artery stenosis.
Medical treatment does not correct the underlying ischemia of the
affected kidney, and decreases in systemic blood pressure may
further aggravate loss of renal function. Progression of
atherosclerotic renal artery disease can be slowed by control of
all modifiable risk factors, including the use of statin drugs for
aggressive lowering of cholesterol. In medically managed persons,
renal function should be followed carefully because deterioration
may be a sign of progressive disease .(1)2.8.Duplex Ultrasound of
the Renal Artery Duplex ultrasonography is noninvasive and does not
use contrast media. Its usefulness extends to persons who have
renal insufficiency or a history of contrast allergy. Performance
of the test does not require discontinuation of any
antihypertensive drug. therapy, and it provides information on
kidney size, screens for obstructive uropathy and aortic aneurysm,
and identifies bilateralrenal artery stenosis. Overlying bowel gas
or other technical problems limit the complete study of both renal
arteries in up to 50% of cases. Often, accessory or branch vessel
disease is not identified. The sensitivity and specificity are 75%
to 80%.(1)2.8.1.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 beforeopening 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 wedge-shaped areas without
color coding (high but artifact-free gain, low pulse repetition
frequency).(2)2.8.2.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)
Figure 2.4 : Renal artery stenosis. A, Intrarenal spectral
waveform shows a tardus-parvus signal with a prolonged acceleration
time and low resistive index (RI). B, Waveform at the origin of the
renal artery from the aorta shows a high peak velocity of 410
cm/sec with an RI of 0.43.(6)
2.8.3.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)
table (2.1): Causes of increased RI in renal arteries. (6)
Table( 2.2) : Different sonographic criteria used for diagnosing
renal artery stenosis.(2)
2.9. Background Comparative Studies The average incidence of
renovascular hypertension is 1 to 4%in an unselected population
(von Bockel et al. 1989; Foster et al. 1973; Olbricht et al. 1991)
but incidences as low as 0.18% and as high as 20% have also been
reported (Arlart and Ingrisch 1984; Tucker and Lebbarthe 1977).
These discrepancies are due to the use of different screening
methods and the investigation of different groups of the normal
population and patients (presence of vascular risk factors and
accompanying diseases, selected patient groups).(2) Hansen et al,
used ultrasonography to screen 870 people over age 65 and found a
lesion (a narrowing of more than 60%) in 6.8%.(2) A population
based study in Denemark about the prevalence of renal artery
stenosis in subjects with moderate to severe hypertension by
Andersen UB , Borglykke A, and Jorgensen T, examined 332 subjects
aged 50-66 years using doppler ultrasound, with blood pressure