Renovascular Hypertension Workup
- Author: Rebecca J Schmidt, DO, FACP, FASN; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
It is useful to determine the clinical risks for renovascular hypertension (RVHT) before embarking on an extensive workup that may not be productive or cost-effective. Patients in whom a definitive noninvasive or invasive workup is indicated are those in whom suggestive clinical features have been identified in the course of the history and physical examination (see Presentation).
At present, no sufficiently accurate, noninvasive, radiologic, or serologic screening test is available that, if negative, completely excludes the presence of renal artery stenosis (RAS). Current guidelines of the American College of Cardiology (ACC) and the American Heart Association (AHA) advocate screening for RAS only for patients in whom a corrective procedure would be considered if renovascular disease were detected.
Guidelines from the ACC/AHA and the European Society of Cardiology (ESC) recommend performing diagnostic studies to identify RAS in patients with any of the following[2, 6] :
Onset of hypertension before the age of 30
Onset of severe hypertension after the age of 55
Accelerated hypertension (sudden and persistent worsening of previously controlled hypertension)
Resistant hypertension (failure of blood-pressure control despite full doses of an appropriate three-drug regimen including a diuretic)
Malignant hypertension (hypertension with coexistent end-organ damage; ie, acute kidney injury, flash pulmonary edema, hypertensive left ventricular failure, aortic dissection, new visual or neurological disturbance, and/or advanced retinopathy)
New azotemia or worsening renal function after the administration of an angiotensin-converting enzyme (AC)E inhibitor or an angiotensin receptor blocker (ARB)
Unexplained atrophic kidney or size discrepancy of greater than 1.5 cm between the kidneys
Unexplained renal failure
The ACC/AHA guidelines also include patients with sudden, unexplained pulmonary edema in its class I recommendations. The ESC has additional recommendation for patients with hypertension and abdominal bruit as well as those with hypertension and hypokalemia in particular when receiving thiazide diuretics.
Various laboratory studies are mentioned (see below), largely for historical background, but these are no longer universally considered useful as screening tests. Therefore, the clinical index of suspicion remains the primary determinant of the degree of evaluation that is indicated for RVHT.
As a screening test for RAS, the ACC/AHA guidelines recommend duplex ultrasonography. The advantages of duplex ultrasonography include lack of radiation, high sensitivity and specificity, low expense, and ability to be repeated without risk or discomfort to the patient.
Other recommended screening tests include computed tomographic angiography, in patients with normal renal function, and magnetic resonance angiography. When the results of noninvasive screening tests are inconclusive and the clinical index of suspicion is high, catheterangiography is recommended to establish the diagnosis of RAS. In patients at risk, carbon dioxide angiography can determine the presence of a stenosis, and the risk associated with radiocontrast angiography is imposed only on those individuals most likely to benefit.
Tests that are not recommended for RAS screening include captopril renal scintigraphy, selective renal vein renin measurements, plasma renin activity, and measurement of plasma renin activity after captopril administration (the captopril test).
See Imaging in Renal Artery Stenosis/Renovascular Hypertension for a complete discussion of this topic.
For pediatric RVHT, basic diagnostic tests should accomplish the following two objectives:
Detect any unsuspected renal parenchymal disease (because the most common medical cause of hypertension in children is renal disease)
Identify the presence of any end-organ damage due to the hypertension
Patient should be transferred to another facility whenever the testing necessary to confirm or refute the diagnosis of RVHT or to assess the severity of a confirmed diagnosis of RVHT cannot be performed adequately at the current facility.
Basic Laboratory Studies
The 2004 fourth report from the National High Blood Pressure Education Program (NHBPEP) Working Group on Children and Adolescents recommends the following initial tests in children with hypertension :
Complete blood count (CBC)
Urine culture (all girls, selected boys)
Blood urea nitrogen (BUN) levels
Serum creatinine levels
In addition, a fasting lipid panel and fasting glucose level are recommended for the following :
Overweight patients whose blood pressure is at the 90th–94 th percentile
All patients with blood pressure at the 95th percentile or higher
Patients with a family history of hypertension or cardiovascular disease
Children with chronic renal disease
Renal function test results frequently yield normal results in children with renovascular disease, even when the lesions are bilateral. Findings on a 24-hour urine study should also be within the reference range in renovascular hypertension.
The CBC, serum electrolyte levels, BUN levels, and serum creatinine levels should indicate whether a pattern of renal function impairment or a pattern of aldosteronoma is present.
Measure a 24-hour urine sample for electrolytes, creatinine, vanillylmandelic acid, catecholamines, 17-hydroxy steroids, and 17-keto steroids. Normal results should rule out the possibility of a medullary or cortical tumor.
The erythrocyte sedimentation rate (ESR) is a good indicator of active arteritis.
One study found that nearly 90% of renal artery disease was detected when patients were pretreated with furosemide. However, these findings can also be misleading, especially in bilateral disease.
Assessment of Renin Release
Plasma renin activity
The baseline plasma renin activity (PRA) is elevated in 50-80% of patients with RVHT. Renin levels may be increased or decreased by all antihypertensive agents. Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease plasma renin levels. Measuring the rise in the PRA 1 hour after administering 25-50 mg of captopril can increase the predictive value of the test. Patients with RAS have an exaggerated increase in PRA, perhaps due to removal of the normal suppressive effect of high angiotensin II levels on renin secretion in the stenotic kidney.
The sensitivity and specificity of studies of the captopril renin test are 75-100% and 60-95%, respectively. Limitations include the need to discontinue antihypertensive medications that can affect the PRA (eg, ACE inhibitors, beta-blockers, and diuretics), the low sensitivity, and the somewhat decreased predictive value when compared to a renogram after ACE inhibition.
Although elevation of peripheral or renal vein PRA has been used to diagnose unilateral renal disease and predict surgical curability, an elevated plasma renin level does not establish the cause of hypertension, and levels that are within the reference range do not rule out renovascular disease.
Renal vein renin ratio
Renal vein renin measurements compare renin release from the 2 kidneys and are used to predict the potential success of surgical revascularization. Renin secretion is increased in the ischemic kidney but is suppressed in the contralateral kidney is suppressed, as evidenced by the similar levels of renin measured in the renal artery (infrarenal inferior vena cava) and the renal vein.
The ratio of the measurement from the ischemic kidney to the measurement from the contralateral kidney is the renal vein renin ratio. A ratio higher than 1.5 constitutes a positive test result and is suggestive of functionally important renovascular disease. Volume depletion exaggerates reduced renal perfusion and may increase the renal vein renin ratio in asymmetric disease.
Fewer than 10% of healthy patients have a renal vein renin ratio higher than 1.5, and less than 20% have a ratio lower than 1.1. It has been suggested that the accuracy of these measurements can be enhanced by prior administration of an angiotensin-converting enzyme (ACE) inhibitor, which will increase renin secretion on the affected side.
False-negative and false-positive results are common. Although more than 90% of patients with unilateral RAS and lateralizing renin values respond positively to angioplasty or surgery, about 50% of those with nonlateralizing findings also benefit from correction of the stenosis.
As a result, most physicians rely on the clinical index of suspicion rather than on renal vein renin measurements to estimate the physiologic significance of a stenotic lesion. An exception may occur in patients with bilateral RAS, in whom renal vein renin measurements can be used to determine the side that most contributes to the hypertension.
When renovascular hypertension is suspected, the standard diagnostic study is renal arteriography. Because this is a highly invasive procedure, it is frequently necessary to perform less specific tests to refine the level of suspicion for renovascular disease before submitting the patient to this test. Some consider intra-arterial DSA to be equally acceptable as a standard.
MRA, CT angiography, and spiral angiography are newer studies that hold considerable promise for diagnosis and evaluation of RVHT. However, they have not yet been investigated sufficiently to permit recommendation of their use in children with renovascular disease. At present, interpretation of the images is technically difficult, and the usefulness of these modalities appears limited to imaging of main vessels.
Selective renal arteriography is still widely considered the standard for diagnosis of RVHT. Renal arteriography is necessary whenever surgery or percutaneous transluminal angioplasty is anticipated. Adding DSA technology to renal arteriography requires one half the volume of dilute contrast medium that standard arteriography requires, while yielding comparable results. Use abdominal pressure and glucagon to prevent bowel motion and gas from affecting the image quality.
Digital subtraction angiography
Intra-arterial DSA is now often recommended as an initial test in this setting. Because intra-arterial DSA requires less radiocontrast (25-50 mL) than conventional angiography (100 mL), it is preferred for patients with compromised renal function. RAS of 70% or more or stenosis of 50% with poststenotic dilatation is considered hemodynamically significant.
Intravenous (IV) DSA has also been suggested for identification of renovascular disease. It is less invasive than intra-arterial DSA but requires more radiocontrast. Yield depends on the skill of the individual interpreting the radiograph, and image quality is diminished by interference from patient or intestinal motion or gas (which can be reduced by abdominal pressure and glucagon), as well as by overlying vessels and poor cardiac output. Compared with arterial studies, IV DSA has a sensitivity and specificity of 90% or less and thus is not commonly used.
Carbon dioxide angiography
Carbon dioxide digital angiography is used as an effective alternative to radiocontrast angiography in patients with renal insufficiency. Carbon dioxide angiography allows gross assessment of the presence of a stenotic lesion. If angioplasty or surgical intervention is to be carried out, subsequent traditional radiocontrast angiography is required to outline the lesions; however, carbon dioxide angiography allows patients to be identified without the risk of dye-related renal injury.
Magnetic resonance angiography
MRA is increasingly reported to provide better results than noninvasive screening procedures. Studies indicate that 3-dimensional MRA with gadolinium-based contrast agents (which are potentially nephrotoxic) has a sensitivity of 96-100% and a specificity of 71-96% for the detection of a main RAS of greater than 50% (see the image below).[9, 10]
When combined with cardiac synchronization, 3-dimensional MRA can sharply delineate the entire length of the major renal arteries. However, it remains suboptimal for the detection of hemodynamically significant lesions of distal, intrarenal, and accessory renal arteries, which, for all purposes, behave pathophysiologically as RAS. MRA is also of limited value in fibromuscular dysplasia (FMD), in which the lesions, being primarily middle and distal, are less well visualized with this modality.
Correlations between MRA and DSA are reported to exceed 90% for accuracy, sensitivity, and specificity. However, the use of gadolinium as an enhancing agent in MRA has been linked to the development of nephrogenic systemic fibrosis in patients with poor renal function. Hence, MRA is an attractive alternative only for patients without renal disease who are not at risk for contrast injury.
Limitations of MRA include relatively high cost and restricted availability. Contraindications to MRA include reduced renal function (estimated glomerular filtration rate [GFR] below 30 mL/min), claustrophobia, and patients with a metallic implant (eg, a pacemaker or surgical clip). The risk-to-benefit ratio should be carefully considered in patients with moderately reduced renal function (estimated GFR, 30-60 mL/min).
Blood oxygen level-dependent MRI
Blood oxygen level-dependent (BOLD-MRI) is a new technique that uses the contrasting paramagnetic properties of oxyhemoglobin and deoxyhemoglobin to depict tissue oxygenation without the need for contrast material. The magnetic rate of relaxation (R2) correlates positively with deoxyhemoglobin levels to measure tissue oxygenation and thus can detect ischemia. Images are obtained at baseline and following administration of an agent that decreases renal oxygen consumption, such as furosemide. Poststenotic kidneys that appear normal on imaging despite high-grade RAS (ie, viable kidney) display a greater-than-normal decrease in R2 after administration of furosemide. Larger studies are needed to confirm the role of BOLD-MRI in identifying patients mostly likely to benefit from revascularization.
Spiral CT with angiography
Spiral CT using small amounts of IV contrast (ie, CT angiography) combines the diagnostic accuracy of arteriography with the lower risk of renal injury of DSA.
The sensitivity and specificity of spiral CT for detecting RAS are approximately 98% and 94%, respectively. In patients with a plasma creatinine concentration higher than 1.7 mg/dL (150 µmol/L), the accuracy is lower (93% sensitivity, 81% specificity), possibly as a consequence of reduced renal blood flow.
Many authors believe that diagnostic imaging should begin with Doppler ultrasonography of the kidneys and abdomen, which is useful in identifying renal disease and abdominal masses. This technique potentially can detect both unilateral and bilateral disease and also can be used to detect recurrent stenosis in patients previously treated with angioplasty or surgery. It should be kept in mind, however, that renal ultrasonographic findings are insufficient to rule out the need for angiography.
Doppler ultrasonography provides both anatomic and functional assessment of the renal arteries. Direct visualization of the main renal arteries (B-mode imaging) is combined with measurement (via Doppler) of intrarenal pressures and velocities (by waveform) to achieve a sensitivity of 72-92% for detecting RAS of 70% or greater.
Doppler ultrasonographic evaluation of renal resistance indices (1 – end diastolic velocity/maximum systolic velocity × 100) can be used to classify patients as potential responders or nonresponders to intervention (ie, a renal resistance index exceeding 80% implies a low likelihood that correction of the stenosis will eventuate in improved blood pressure control or renal function).
Important disadvantages of this modality include the possibility that bowel gas can interfere with direct visualization of the renal arteries (50-90% of the time). Doppler measurements are hampered very infrequently (0-2%). Furthermore, this modality is time-consuming to perform (requiring approximately 2 hours) and is a technically difficult procedure with a steep learning curve, making success highly operator-dependent.
Because of its high false-negative rate (20-25%), the nonstimulated renal scan has limited efficacy and is not universally recommended as a screening test. The predictive value of radioisotope scanning, however, can be enhanced by the administration of captopril orally (25-50 mg) 1 hour before the isotope is injected. Decreased function after treatment with captopril indicates a high likelihood of renovascular stenosis. If the scan findings remain normal, renovascular disease is not ruled out.
Removal of angiotensin II–mediated vasoconstriction by ACE inhibition induces a decline in the GFR of the stenotic kidney and often an equivalent increase in the GFR of the contralateral kidney. The difference in the GFR between the 2 kidneys is enhanced by radioisotope and is visible on the renogram.
A marker of glomerular filtration (eg, diethylenetriamine pentaacetic acid [DTPA]) or compounds that are secreted by the proximal tubule (eg, hippurate, mercaptotriglycylglycine [MAG-3]) can be used to estimate total, as well as differential, kidney function—information that may be useful in the assessment of treatment options. The latter may be more reliable in patients with renal insufficiency.
Positive results from an ACE inhibitor renogram are determined according to the following 2 criteria:
Relative uptake of the isotope decreased, with 1 kidney accounting for less than 40% of the total GFR
Peak uptake of the isotope delayed to more than 10-11 minutes (normal, 3-6 minutes)
A slower washout of the isotope may occur in the stenotic kidney, as demonstrated in unilateral RAS by a delay of 5 minutes or longer in washout on the involved side. This criterion may be evaluated best with a compound such as hippurate, which is secreted into the tubules rather than only being filtered.
IV pyelography (IVP) is mentioned primarily because of its historical significance. It has a sensitivity of only 75-80%; thus, a negative test result cannot exclude RVHT reliably. Furthermore, it is often unhelpful when bilateral disease is present; bilateral disease can be missed if a small difference exists between the 2 kidneys. Major findings on IVP that suggest unilateral ischemia include decreased renal size and delayed caliceal appearance time in comparison with the contralateral kidney. Results of IVP are often inaccurate in children.
Chest radiography and echocardiography may be helpful in differentiating left ventricular failure from chronic hypertension.
Because many of the lesions in FMD occur at the renal artery orifice, obtaining a good histologic sample is frequently difficult. Evaluation of stenotic lesions invariably reveals the characteristic FMD in the medial or perimedial muscular layers, associated with varying degrees of intimal hyperplasia.
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