eMedicine Specialties > Nephrology > Hypertension and the Kidney

Renovascular Hypertension: Differential Diagnoses & Workup

Author: Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Coauthor(s): Sandeep S Soman, MBBS, MD, DNB, Senior Staff Physician, Department of Internal Medicine, Division of Nephrology and Hypertension, Henry Ford Hospital
Contributor Information and Disclosures

Updated: Sep 4, 2009

Differential Diagnoses

Hypertension

Other Problems to Be Considered

Other nonessential forms of hypertension
Essential hypertension

Workup

Laboratory Studies

• Characterizing the clinical risks for RVHT before embarking on an extensive workup that may not be productive or cost effective is useful. Patients in whom a definite noninvasive or invasive workup is indicated are those with the clinical features described in History and Physical. 
• A schematic approach to the diagnostic investigation of RAS is shown in the image below and in Image 3.

• The criterion standard to establish a diagnosis of RAS is renal arteriography.  The lab studies are mentioned for historical background but are no longer universally considered useful as screening tests.
• 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 PRA. 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, diuretics), the low sensitivity, and the somewhat decreased predictive value when compared to a renogram after ACE inhibition.
• Renal vein renin measurements  
• Renal vein renin measurements compare renin release from each kidney and are used to predict the potential success of surgical revascularization. Increased renin secretion in the ischemic kidney as compared to the contralateral kidney, that is, a renal vein renin difference of 1.5-fold, constitutes a positive test result and suggests that revascularization will treat elevated blood pressure successfully. Renin secretion in the contralateral kidney is suppressed, as evidenced by the similar levels of renin measured in the renal artery (infrarenal inferior vena cava) and renal vein.
• Fewer than 10% of healthy patients have a ratio above 1.5 and fewer than 20% have a ratio below 1.1. The accuracy of these measurements has been suggested to be enhanced by the prior administration of an 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 have a positive response to angioplasty or surgery, approximately 50% with nonlateralizing findings also benefit from correction of the stenosis. As a result, most physicians rely on the clinical index of suspicion rather than 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 renins can be used to determine the side that most contributes to the hypertension.
• Screening: Guidelines of the AmericanCollege of Cardiology and the American Heart Association advocate screening for RAS only for patients in whom a corrective procedure would be considered if renovascular disease was detected.

Imaging Studies

• Angiography  
• A conventional renal angiogram or an intra-arterial digital subtraction angiogram (DSA) remains the diagnostic criterion standard among available tests for detecting renal artery occlusive disease. Because intra-arterial DSA requires less radiocontrast (25-50 mL) than conventional angiography (100 mL), it is preferred for patients with compromised renal function. A RAS of greater than or equal to 70% or a stenosis of 50% with poststenotic dilatation is considered hemodynamically significant.
• Intravenous DSA is less invasive but requires more radiocontrast than intra-arterial DSA. Its sensitivity and specificity are 90% or less as compared to arterial studies; hence, it is no longer used.
• Carbon dioxide digital angiography is used as an effective alternative to iodinated radiocontrast material in patients with renal insufficiency. Carbon dioxide angiogram allows a gross assessment of the presence of a stenotic lesion. Angioplasty and/or surgical intervention require subsequent traditional radiocontrast angiography to specifically outline the lesions; however, with carbon dioxide angiography, patients can be identified without the risk of dye-related renal injury.
• Magnetic resonance angiography
• Magnetic resonance angiography (MRA)¹ is increasingly reported to provide better results than the noninvasive screening procedures mentioned in Lab Studies.  Studies indicate that 3-dimensional MRA with gadolinium-based contrast agents² (which have potential for nephrotoxicity) has a sensitivity of 96-100% and a specificity of 71-96% for the detection of a main RAS of greater than 50%.
• When combined with cardiac synchronization, 3-dimensional MRA can sharply delineate the entire length of the major renal arteries (see image below and Image 1); however, MRA remains suboptimal for the detection of hemodynamically significant lesions of distal, intrarenal, and accessory renal arteries, which, for all purposes, behave pathophysiologically as RAS, and it is also of limited value in fibromuscular dysplasia, where lesions, by being primarily middle and distal, are less well visualized by MRA.
  
  Correlations between MRA and digital subtraction angiography are reported to exceed 90% for accuracy, sensitivity, and specificity. However, the use of gadolinium as an enhancing agent in MR procedures 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 include cost and technique availability. Contraindications to MRA include reduced renal function (estimated GFR <30 mL/min), claustrophobia, and patients with a metallic implant, such as a pacemaker or surgical clip. The risk-benefit ratio should be carefully considered in patients with moderately reduced renal function (estimated GFR 30-60 mL/min).
• Spiral CT scan with angiography  
• SpiralCT scans using small amounts of IV contrast (ie, CT angiography) offer the diagnostic accuracy of arteriography and the lower risk of renal injury with IV digital subtraction angiography.
• Sensitivity and specificity of the spiral CT scan 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 due to reduced renal blood flow.
• Doppler ultrasonography  
• Doppler ultrasonography provides both anatomical 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 the detection of RAS exceeding 70%. Doppler ultrasonographic evaluation of renal resistance indices (1-end diastolic velocity/maximum systolic velocity X 100) can be used to classify patients as potential responders or nonresponders to intervention (ie, a renal resistance index exceeding 80% infers a low likelihood that correction of the stenosis will eventuate in improved blood pressure control or renal function).
• 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.
• Important disadvantages of this modality include the potential 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 (requires approximately 2 h) and is a technically difficult procedure with a steep learning curve, making success highly operator dependent.
• A promising screening test, intrarenal echo Doppler velocimetric indices, is currently under investigation.
• Renogram and captopril 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. 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 when assessing treatment options. The latter may be more reliable in patients with renal insufficiency.
• Positive results from ACE inhibitor renogram are determined by the following 2 criteria: (1) decreased relative uptake of isotope, with 1 kidney accounting for less than 40% of the total GFR and (2) delayed peak uptake of the isotope of more than 10-11 minutes (normal is 3-6 min).
• Note that a slower washout of the isotope may occur in the stenotic kidney, which is 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.

Other Tests

• The IV pyelogram is mentioned as a test of historical significance. It has a sensitivity of only 75-80%; thus, a negative test result cannot exclude RVHT reliably. Furthermore, bilateral disease can be missed if a small difference exists between the 2 kidneys. Major findings on IV pyelography that suggest the presence of unilateral ischemia include decreased renal size and delayed caliceal appearance time when compared to the contralateral kidney.
• Selecting the appropriate test
  • At present, no sufficiently accurate, noninvasive, radiologic, or serologic screening test is available that, if negative, completely excludes the presence of RAS. Therefore, clinical index of suspicion remains the primary determinant for the degree of evaluation (see image below and Image 3).

• When the history is highly suggestive and no risk for radiocontrast-mediated renal injury is present, an intra-arterial DSA or conventional angiogram (criterion standard) is the appropriate initial test. In patients at risk, a carbon dioxide angiogram can determine the presence of a stenosis, and the risk of radiocontrast angiogram is imposed only on those individuals most likely to benefit.
• Perform a spiral CT scan, MRA, or duplex ultrasonography (depending on availability and local experience) when moderate suspicion of renovascular disease exists. A negative test result indicates that RAS is highly unlikely, while a positive test result can be followed by renal arteriography.

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