Renovascular Hypertension Workup

Updated: Dec 01, 2020
  • Author: Rebecca J Schmidt, DO, FACP, FASN; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Workup

Approach Considerations

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). [20] 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. [3]   Testing is not recommended in patients whose hypertension is responsive to medication and those in whom there is not a high likelihood of clinically significant renovascular disease. 

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 [3, 21] :

  • 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 (ACE) 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 thought to be a consequence of renovascular disease

The ACC/AHA guidelines also include patients with sudden, unexplained pulmonary edema in its class I recommendations. [3] The ESC recommendation include patients with hypertension and abdominal bruit as well as those with hypertension and hypokalemia in particular when receiving thiazide diuretics. [21]

 

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Screening

As a screening test for RAS, the ACC/AHA guidelines recommend duplex ultrasonography. [3]  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. [22]   Disadvantages include that it is time consuming, operator dependent, and technically difficult in obese patients.

Other recommended screening tests include computed tomographic angiography (CTA), 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, angiography is recommended to establish the diagnosis of RAS. [3]  However, because of the risks 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). [3]

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

Patients should be transferred to another facility whenever the current facility lacks the capacity to perform the testing necessary to confirm or refute the diagnosis of RVHT or to assess the severity of a confirmed diagnosis of RVHT.

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 kidney function). [23, 24, 25]

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.

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Laboratory Studies

Laboratory studies mentioned are often done for completeness and for historical context and are not considered useful as screening tests. Initial tests for both adults and children with hypertension include [26] :

In addition, a fasting lipid panel and fasting glucose level are recommended for the following [26] :

  • 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 RVHT.

The CBC, serum electrolyte levels, BUN levels, and serum creatinine levels should indicate the presence of renal function impairment or whether a pattern of hyperaldosteronism is present.

A 24-hour urine sample for electrolytes, creatinine, vanillylmandelic acid, catecholamines, 17-hydroxy steroids, and 17-keto steroids should be considered in patients with elevated blood pressure that is not typical of essential hypertension or RVHT.  Normal results should rule out the possibility of a medullary or cortical tumor.

The erythrocyte sedimentation rate (ESR) may be elevated in active arteritis.

 

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Imaging Studies

Selective renal arteriography is still widely considered the gold standard for diagnosis of RVHT. Renal arteriography is necessary whenever surgery or percutaneous transluminal angioplasty is anticipated.  Because this is a highly invasive procedure, it is appropriate to perform screening and less specific tests in order to refine the level of suspicion for disease that might me amenable to treatment.

Computed tomographic angiography

Spiral CT scan with intravenous contrast (CT angiography) is highy accurate in diagnosing atherosclerotic renovascular disease. [27]   Adding digital subtraction angiography (DSA) technology to renal arteriography requires one half the volume of dilute contrast medium that standard arteriography requires, while yielding comparable results.  Because intra-arterial DSA requires less radiocontrast (25-50 mL) than conventional angiography (100 mL), it is preferred for patients with compromised kidney 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.

Magnetic resonance angiography

MRA is increasingly reported to provide better results than noninvasive screening procedures. [28]  Studies indicate that 3-dimensional MRA with gadolinium-based contrast agents 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). [29, 30, 31]  Concerns for severe dermatologic side effects when used in patients with reduced kidney function have led to avoidance of these agents though recent studies favor a more permissive approach with certain types of gadolinium-based contrast. [32, 33]

Magnetic resonance angiography (MRA) showing renal Magnetic resonance angiography (MRA) showing renal artery stenosis. Courtesy of Patricia Stoltzfus, MD, Chief of Interventional Radiology, West Virginia University.

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.

Limitations of MRA include relatively high cost, restricted availability and concerns for long-term dermatologic side effects when used in patients with poor kidney function. Contraindications to MRA include claustrophobia and the presence of a metallic implant (eg, a pacemaker or surgical clip). The risk-to-benefit ratio should be carefully considered in patients with reduced kidney function and in patients on hemodialysis should be dialyzed daily for three days after receipt of this agent.

 

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Other Tests

Renogram

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.

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.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.

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.

While the availability of more sophisticated imaging along with a number of limitations have relegated the renogram away from favor as a screening test for RVHT, it remains useful for determining differential (relative) function of each kidney in settings where a nephrectomy is contemplated.

Plasma renin activity

The baseline plasma renin activity (PRA) is elevated in 50-80% of patients with RVHT [37]. 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 [37].

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 [38].

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, 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. [34] 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. [10]

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. [10]

Carbon dioxide angiography

Carbon dioxide gas has been used in combination with iodinated contrast agents for angiography in the treatment of RAS, including post-transplant RAS, since late 1990s, with some success. [63, 64, 65, 66]  This approach allows a reduction in the amount of iodinated contrast needed, thus decreasing the risk of contrast-induced acute kidney injury.

Carbon dioxide angiography is not completely risk free, however; it has been linked to mesenteric ischemia, non-fatal myocardial infarction, and respiratory failure, and its use in procedures above diaphragm is contraindicated. [67]  The increased availability of low osmolar agents along with lack of training in the use of this modality has likely led to its infrequent use, though it remains an option for patients at higher risk of contrast-associated acute kidney injury.

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