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