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==Overview==
==Overview==
Several clinical clues aid in the suspicion of ARAS and warrant further investigation. To date, imaging is considered the optimal modality to diagnose ARAS. According to the ACC/AHA guidelines in 2013, Doppler ultrasonography, CT angiography, and MR angiography are all non-invasive techniques to diagnose ARAS. Renal angiography remains the gold standard for diagnosis of ARAS. Nonethetheless, it is an invasive procedure that should be reserved to patients who are planning to perform a catheterization procedure and concede to renal angiography or to patients whose non-invasive imaging was equivocal.
Several clinical clues aid in the suspicion of ARAS and warrant further investigation. To date, imaging is considered the optimal modality to diagnose ARAS. According to the ACC/AHA guidelines in 2013, Doppler ultrasonography, CT angiography, and MR angiography are all non-invasive techniques to diagnose ARAS. Renal angiography remains the gold standard for diagnosis of ARAS. Nonethetheless, it is an invasive procedure that should be reserved to patients who are planning to perform a catheterization procedure and concede to renal angiography or to patients whose non-invasive imaging was equivocal.
Magnetic resonance angiography (MRA), helical computed tomographic angiography (CTA), Doppler ultrasonography, renal scintigraphy (ie, captopril scan), invasive angiography, peripheral renin levels, and renal vein renin sampling have all been used as screening tests to detect ARAS. Renal vein renin sampling, peripheral renin levels, and renal scintigraphy are not generally recommended for ARAS screening because of their low sensitivity and low specifity.38-40
For an imaging study to be considered optimal, the following 4 objectives must be met: (1) ARAS must be detected and characterized on the basis of anatomic and hemodynamic severity; (2) anatomic consequences of ARAS on the artery itself and on the kidney must be assessed (eg, severe ARAS can result in poststenotic dilatation of the artery, which can be detected by CTA and MRA, and also in shrinkage of the renal parenchyma, with the kidney being <8 cm); (3) functional and cellular consequences of ARAS on the kidney must be evaluated (eg, functional data can be obtained via the abnormal intrarenal transit of gadolinium during magnetic resonance imaging with use of captopril, future studies are assessing the ability of diffusion-weighted magnetic resonance imaging to determine the cellular viability of renal parenchyma tissue in patients with chronic kidney disease; and (4) criteria associated with renal impairment related to renovascular disease must be identified).41
Ultrasonography
Ultrasonography is widely available, safe, and inexpensive and consequently is typically the first imaging study used to detect ARAS. However, results are operator dependent, with accuracy ranging from 60% to 90%; the entire length of the renal artery or an accessory renal artery can be overlooked, and thus the stenotic lesion will be missed.42
Information on size of the kidneys, renal functional reserve, and renal resistive index (RRI [defined as peak systolic velocity – end-diastolic velocity/peak systolic velocity]) can be obtained with ultrasonography.43 A high renal artery end-diastolic velocity (>90 cm/s) and low RRI (<75-80) indicate no microvascular disease or increased resistance.39,44
Spectral broadening and increased velocity on ultrasonography are markers of hemodynamically significant stenoses. For example, a renoaortic velocity ratio (defined as the renal artery peak systolic velocity/aortic peak systolic velocity) greater than 3.5 has been correlated to 60% stenosis,45 whereas a renal artery peak systolic velocity greater than 150 cm/s correlates to 50% stenosis, and a velocity greater than 180 cm/s correlates to 60% stenosis.45-48 A literature review found that the sensitivity and specificity of ultrasonography were 85% and 92%, respectively, in detecting hemodynamically significant ARAS.49
Severe stenoses can produce tardus-parvus spectral changes on Doppler ultrasonography, revealed as a slowed systolic acceleration with a decreased resistive index.50,51 Quantitative criteria proposed for the diagnosis of distal stenoses include blunting of early systolic peak acceleration (<3 m/s2), an acceleration index greater than 4 m/s2, increase in time to systolic peak (>0.07 s), or greater than 5% difference in RRI between kidneys. However, because of the difficulty in interpretating these complex waveforms, these criteria are seldom used.52-54
Computed Tomographic Angiography
The possibility of 3-dimensional reconstructions has made CTA an important tool in the diagnosis of ARAS. Because CTA involves use of ionizing radiation and iodinated contrast medium, it is contraindicated in patients with contrast allergy. Patients with impaired renal function can develop contrast-induced nephropathy if iodinated contrast is used, but generous fluid hydration before contrast administration can effectively prevent this complication. For detection of ARAS, the sensitivity of CTA is 94%; the specificity varies between 60% and 90%.55,56
Compared to MRA, CTA can detect small accessory renal arteries because of its high spatial resolution. It is also preferred for patients who have implanted devices, for patients with limited breath-hold capacity (requiring shorter acquisition times), and for patients with claustrophobia. However, CTA has less specificity than MRA for detecting hemodynamically significant ARAS; it cannot be used safely in patients with borderline renal dysfunction because of the necessity of iodinated contrast agents; images obtained with CTA are difficult to interpret in heavily calcified arteries, and CTA requires use of ionizing radiation.57
Magnetic Resonance Angiography
Magnetic resonance angiography has a reported sensitivity and specificity of 90% to 100%55,56 and does not require use of iodinated contrast or radiation. Gadolinium-based contrast medium should be avoided in patients with moderate to end-stage renal failure because of the risk of nephrogenic systemic fibrosis. Additionally, MRA should not be used in patients with certain implanted devices (ie, pacemakers, defibrillators, cochlear implants, and spinal cord stimulators) or in claustrophobic patients. Unlike CTA, MRA has no calcification artifact, neither iodinated contrast medium nor radiation is used, and contrast reaction rates are lower.1
Angiography
Invasive renal arteriography is helpful in evaluating ARAS. In addition to assessing the severity of ARAS, angiography can detect intrarenal vascular abnormalities and anatomic abnormalities of the kidneys, renal arteries, and aorta. Digital subtraction angiography improves contrast resolution and may decrease the volume of contrast needed to as little as 15 mL. However, because renal angiography is invasive, there are risks associated with arterial puncture and manipulation of the catheter/wire, which can result in arterial trauma, spasm, or thromboembolic phenomenon.58 In patients with renal impairment or contrast allergy, carbon dioxide can be used as a nonnephrotoxic contrast agent.
The early work by White et al59 established that there is substantial intra- and interobserver variability in the visual estimation of coronary stenoses, which likely also applies to the visual estimation of ARAS. Therefore, relying solely on angiography to visually estimate the severity of ARAS is suboptimal, and adjunctive tools should be used to determine whether renal ischemia is present.
Translesional pressure gradients can be measured across areas of stenosis to determine hemodynamic significance (if there is doubt) before performing therapeutic procedures such as percutaneous transluminal renal angioplasty (PTRA) or stenting. In a small case series, Mangiacapra et al60 measured translesional pressure gradients using papaverine and dopamine to induce renal hyperemia in 53 consecutive patients before PTRA. They found that patients with the most substantial improvement in hypertension were those with a translesional gradient greater than 20 mm Hg (corresponding to a distal-proximal pressure ratio of 0.79 as the optimal cutoff). De Bruyne et al61 demonstrated that stenoses with a distal to proximal renal artery pressure decrease greater than 10% were associated with increased renin production, suggesting that measurement of translesional pressure gradients might help identify hemodynamically significant ARAS.


==Diagnosis==
==Diagnosis==

Revision as of 23:04, 9 December 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul,Serge Korjian

Overview

Several clinical clues aid in the suspicion of ARAS and warrant further investigation. To date, imaging is considered the optimal modality to diagnose ARAS. According to the ACC/AHA guidelines in 2013, Doppler ultrasonography, CT angiography, and MR angiography are all non-invasive techniques to diagnose ARAS. Renal angiography remains the gold standard for diagnosis of ARAS. Nonethetheless, it is an invasive procedure that should be reserved to patients who are planning to perform a catheterization procedure and concede to renal angiography or to patients whose non-invasive imaging was equivocal.




Magnetic resonance angiography (MRA), helical computed tomographic angiography (CTA), Doppler ultrasonography, renal scintigraphy (ie, captopril scan), invasive angiography, peripheral renin levels, and renal vein renin sampling have all been used as screening tests to detect ARAS. Renal vein renin sampling, peripheral renin levels, and renal scintigraphy are not generally recommended for ARAS screening because of their low sensitivity and low specifity.38-40

For an imaging study to be considered optimal, the following 4 objectives must be met: (1) ARAS must be detected and characterized on the basis of anatomic and hemodynamic severity; (2) anatomic consequences of ARAS on the artery itself and on the kidney must be assessed (eg, severe ARAS can result in poststenotic dilatation of the artery, which can be detected by CTA and MRA, and also in shrinkage of the renal parenchyma, with the kidney being <8 cm); (3) functional and cellular consequences of ARAS on the kidney must be evaluated (eg, functional data can be obtained via the abnormal intrarenal transit of gadolinium during magnetic resonance imaging with use of captopril, future studies are assessing the ability of diffusion-weighted magnetic resonance imaging to determine the cellular viability of renal parenchyma tissue in patients with chronic kidney disease; and (4) criteria associated with renal impairment related to renovascular disease must be identified).41

Ultrasonography Ultrasonography is widely available, safe, and inexpensive and consequently is typically the first imaging study used to detect ARAS. However, results are operator dependent, with accuracy ranging from 60% to 90%; the entire length of the renal artery or an accessory renal artery can be overlooked, and thus the stenotic lesion will be missed.42

Information on size of the kidneys, renal functional reserve, and renal resistive index (RRI [defined as peak systolic velocity – end-diastolic velocity/peak systolic velocity]) can be obtained with ultrasonography.43 A high renal artery end-diastolic velocity (>90 cm/s) and low RRI (<75-80) indicate no microvascular disease or increased resistance.39,44

Spectral broadening and increased velocity on ultrasonography are markers of hemodynamically significant stenoses. For example, a renoaortic velocity ratio (defined as the renal artery peak systolic velocity/aortic peak systolic velocity) greater than 3.5 has been correlated to 60% stenosis,45 whereas a renal artery peak systolic velocity greater than 150 cm/s correlates to 50% stenosis, and a velocity greater than 180 cm/s correlates to 60% stenosis.45-48 A literature review found that the sensitivity and specificity of ultrasonography were 85% and 92%, respectively, in detecting hemodynamically significant ARAS.49

Severe stenoses can produce tardus-parvus spectral changes on Doppler ultrasonography, revealed as a slowed systolic acceleration with a decreased resistive index.50,51 Quantitative criteria proposed for the diagnosis of distal stenoses include blunting of early systolic peak acceleration (<3 m/s2), an acceleration index greater than 4 m/s2, increase in time to systolic peak (>0.07 s), or greater than 5% difference in RRI between kidneys. However, because of the difficulty in interpretating these complex waveforms, these criteria are seldom used.52-54

Computed Tomographic Angiography The possibility of 3-dimensional reconstructions has made CTA an important tool in the diagnosis of ARAS. Because CTA involves use of ionizing radiation and iodinated contrast medium, it is contraindicated in patients with contrast allergy. Patients with impaired renal function can develop contrast-induced nephropathy if iodinated contrast is used, but generous fluid hydration before contrast administration can effectively prevent this complication. For detection of ARAS, the sensitivity of CTA is 94%; the specificity varies between 60% and 90%.55,56

Compared to MRA, CTA can detect small accessory renal arteries because of its high spatial resolution. It is also preferred for patients who have implanted devices, for patients with limited breath-hold capacity (requiring shorter acquisition times), and for patients with claustrophobia. However, CTA has less specificity than MRA for detecting hemodynamically significant ARAS; it cannot be used safely in patients with borderline renal dysfunction because of the necessity of iodinated contrast agents; images obtained with CTA are difficult to interpret in heavily calcified arteries, and CTA requires use of ionizing radiation.57

Magnetic Resonance Angiography Magnetic resonance angiography has a reported sensitivity and specificity of 90% to 100%55,56 and does not require use of iodinated contrast or radiation. Gadolinium-based contrast medium should be avoided in patients with moderate to end-stage renal failure because of the risk of nephrogenic systemic fibrosis. Additionally, MRA should not be used in patients with certain implanted devices (ie, pacemakers, defibrillators, cochlear implants, and spinal cord stimulators) or in claustrophobic patients. Unlike CTA, MRA has no calcification artifact, neither iodinated contrast medium nor radiation is used, and contrast reaction rates are lower.1

Angiography Invasive renal arteriography is helpful in evaluating ARAS. In addition to assessing the severity of ARAS, angiography can detect intrarenal vascular abnormalities and anatomic abnormalities of the kidneys, renal arteries, and aorta. Digital subtraction angiography improves contrast resolution and may decrease the volume of contrast needed to as little as 15 mL. However, because renal angiography is invasive, there are risks associated with arterial puncture and manipulation of the catheter/wire, which can result in arterial trauma, spasm, or thromboembolic phenomenon.58 In patients with renal impairment or contrast allergy, carbon dioxide can be used as a nonnephrotoxic contrast agent.

The early work by White et al59 established that there is substantial intra- and interobserver variability in the visual estimation of coronary stenoses, which likely also applies to the visual estimation of ARAS. Therefore, relying solely on angiography to visually estimate the severity of ARAS is suboptimal, and adjunctive tools should be used to determine whether renal ischemia is present.

Translesional pressure gradients can be measured across areas of stenosis to determine hemodynamic significance (if there is doubt) before performing therapeutic procedures such as percutaneous transluminal renal angioplasty (PTRA) or stenting. In a small case series, Mangiacapra et al60 measured translesional pressure gradients using papaverine and dopamine to induce renal hyperemia in 53 consecutive patients before PTRA. They found that patients with the most substantial improvement in hypertension were those with a translesional gradient greater than 20 mm Hg (corresponding to a distal-proximal pressure ratio of 0.79 as the optimal cutoff). De Bruyne et al61 demonstrated that stenoses with a distal to proximal renal artery pressure decrease greater than 10% were associated with increased renin production, suggesting that measurement of translesional pressure gradients might help identify hemodynamically significant ARAS.




Diagnosis

Indications for Work-Up

According to the 2013 ACC/AHA Guidelines for the Management of PAD[1], diagnostic work-up for renal artery stenosis is indicated in the following conditions:

Class I Recommendations[1]

  • Hypertension of any stage before the age of 30
  • Stage II hypertension (severe hypertension systolic blood pressure > 180 mm Hg or diastolic blood pressure > 120 mm Hg) in patients older than 55 years. If only mild hypertension is present, then renal artery stenosis is the underlying cause in only 1% of patients [2], but if the blood pressure is markedly elevated, then the risk of renal artery stenosis goes up 10 to 50 fold.
  • Accelerated condition of previously controlled hypertension
  • Resistant hypertension
  • Malignant hypertension
  • New azotemia (50% rise in creatinine that is sustained) within one week after administration of an Angiotensin Converting Enzyme (ACE)inhibitor or ARB
  • Unexplained atrophic kidney or asymmetric kidneys that differ by > 1.5 cm. If the kidney is < 9 cm in size, there is a 75% chance that renal artery stenosis is present.
  • Severe hypertension, impaired renal function, and recurrent flash pulmonary edema

Class IIa Recommendations[1]

  • Unexplained renal failure including patients starting renal replacement therapy

Class IIb Recommendations[1]

Other Indications

  • Severe hypertension in the presence of polyvascular disease (coronary artery disease or peripheral arterial disease)
  • A unilateral systolic-diastolic abdominal bruit. Although a bruit is infrequent in documented renal artery stenosis (the sensitivity is only 40% percent) if it is auscultated, it is associated with a very high specificity of 99%.[3]
  • The association of race with renal artery stenosis is not clear. Reports that it is observed more often in white patients may be due to reporting bias.[4]

Diagnostic Methods[1]

The best technique to diagnose atherosclerotic renal artery stenosis (ARAS) is by imaging. Assessment of both the main and the accessory renal arteries bilaterally is important for diagnostic purposes. Further evaluation should include the anatomic location of the stenosis, severity of stenosis, associated perirenal and perivascular pathologies, such as aneurysms or masses.[1] Duplex ultrasonography, computer tomographic angiography (CTA), magnetic resonance angiography (MRA), and catheter angiography are 4 techniques that are currently recommended for the diagnosis of ARAS.[1] In contrast, neither selective renal vein renin studies, captopril renal scintigraphy, plasma renin activity nor the captopril test are recommended anymore.[1]

Duplex Ultrasonography

Diagnosis by Duplex ultrasonography is considered class I recommendation. It may be used as an initial screening tool for diagnosis of ARAS. Ultrasonography might not be very accurate in obese patients or those with intestinal gas.[1]

Computed Tomographic Angiography

Diagnosis by CT angiography is considered class I recommendation. It provides higher spacial resolution compared to magnetic resonanc angiography (MRA). CT angiography may be used in patients with normal renal function to avoid contrast-induced nephropathy in patients with impaired renal function. Presence of previous stents or metallic objects are considered a contraindication for the use of CTA.[1]

Magnetic Resonance Angiography

Diagnosis by MRA is considered class I recommendation. Gadolinium-based MRA has less nephrotoxic characterstics with good visualization of the renal arteries and perirenal pathologies. Presence of previous stents or metallic objects are considered a contraindication for the use of MRA.[1]

Catheter Angiography

Catheter angiography is considered class I recommendation. It is the gold standard for the diagnosis of ARAS. Renal angiography may be used only if previous tests are equivocal and clinical suspicion is high or if the patient is already undergoing another catheterization process and consents to renal angiography. Generally, it is associated with a low frequency of adverse events.[1]

Management of Patients With Peripheral Artery Disease (Compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations) : A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines[5]

Clinical Clues to the Diagnosis of RAS (DO NOT EDIT)[1]

Class I
"1.Onset of hypertension before the age of 30 years or severe hypertension after the age of 55. (Level of Evidence: B)"
"2.Accelerated, resistant, or malignant hypertension. (Level of Evidence: C)"
"3.Development of new azotemia or worsening renal function after administration of an ACE inhibitor or ARB agent . (Level of Evidence: B)"
"4.Unexplained atrophic kidney or size discrepancy between kidneys of greater than 1.5 cm. (Level of Evidence: B)"
"5.Sudden, unexplained pulmonary edema. (Level of Evidence: B)"
Class IIa
"1.Unexplained renal dysfunction, including individuals starting renal replacement therapy. (Level of Evidence: B)"
Class IIb
"1.Multi-vessel coronary artery disease. (Level of Evidence: B)"
"2.Unexplained congestive heart failure. (Level of Evidence: C)"
"3.Refractory angina. (Level of Evidence: C)"

Diagnostic Methods (DO NOT EDIT)[1]

Class I
"1. Duplex ultrasonography is recommended as a screening test to establish the diagnosis of RAS. (Level of Evidence: B)"
"2. Computed tomographic angiography (in individuals with normal renal function) is recommended as a screening test to establish the diagnosis of RAS. (Level of Evidence: B)"
"3. Magnetic resonance angiography is recommended as a screening test to establish the diagnosis of RAS. (Level of Evidence: B)"
"4. When the clinical index of suspicion is high and the results of noninvasive tests are inconclusive, catheter angiography is recommended as a diagnostic test to establish the diagnosis of RAS. (Level of Evidence: B)"
Class III
"1. Captopril renal scintigraphy is not recommended as a screening test to establish the diagnosis of RAS. (Level of Evidence: C)"
"2. Selective renal vein renin measurements are not recommended as a useful screening test to establish the diagnosis of RAS. (Level of Evidence: B)"
"3. Plasma renin activity is not recommended as a useful screening test to establish the diagnosis of RAS. (Level of Evidence: B)"
"4. The captopril test (measurement of plasma renin activity after captopril administration) is not recommended as a useful screening test to establish the diagnosis of RAS. (Level of Evidence: B)"

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH; et al. (2013). "Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Circulation. 127 (13): 1425–43. doi:10.1161/CIR.0b013e31828b82aa. PMID 23457117.
  2. Lewin A, Blaufox MD, Castle H, Entwisle G, Langford H (1985). "Apparent prevalence of curable hypertension in the Hypertension Detection and Follow-up Program". Arch Intern Med. 145 (3): 424–7. PMID 3872106.
  3. Turnbull JM (1995). "The rational clinical examination. Is listening for abdominal bruits useful in the evaluation of hypertension?". JAMA. 274 (16): 1299–301. PMID 7563536.
  4. Svetkey LP, Kadir S, Dunnick NR, Smith SR, Dunham CB, Lambert M; et al. (1991). "Similar prevalence of renovascular hypertension in selected blacks and whites". Hypertension. 17 (5): 678–83. PMID 2022411.
  5. Rooke TW, Hirsch AT, Misra S, Sidawy AN, Beckman JA, Findeiss L; et al. (2013). "Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol. 61 (14): 1555–70. doi:10.1016/j.jacc.2013.01.004. PMC 4492473. PMID 23473760.

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