Laboratory Studies
Obtain serum creatinine levels to assess the level of renal dysfunction. Serum levels can be used to calculate an estimated creatinine clearance based on the Cockcroft-Gault equation or the Modification of Diet in Renal Disease (MDRD) formula. [20]
Perform a 24-hour urine collection, or obtain a protein-creatinine ratio on a random void urine specimen, to more accurately assess the level of renal dysfunction and to measure the degree of proteinuria. Vascular renal disease is more often associated with minimal-to-moderate degrees of proteinuria; levels rarely reach the nephrotic range.
Perform urinalysis to ensure that red blood cells or red blood cell casts (a hallmark of glomerulonephritis) are absent.
Perform serologic tests for systemic lupus erythematosus or vasculitis if these conditions are suggested (eg, antinuclear antibodies, C3, C4, antinuclear cytoplasmic antibodies).
Studies designed to assess the renin-angiotensin system are of little diagnostic utility in patients with atherosclerotic renovascular disease (RVD).
Peripheral renin activity reflects volume status in healthy individuals. It may be elevated in patients with renovascular causes of hypertension and in those with essential hypertension. It is equally nondiscriminatory in patients with atherosclerotic RVD with ischemic nephropathy.
Imaging Studies
Ultrasonography
Renal ultrasonography scanning is performed frequently in patients with renal dysfunction. Ultrasonography scanning is an anatomic, not a functional, test. The only contribution to the entity of renal artery stenosis is a suggestion of the diagnosis when examination results indicate significant asymmetry of kidney size (ie, size discrepancy of >1.5 cm). Additionally, ultrasonography may be useful in detecting the presence of a solitary kidney, in which case, renal artery stenosis of that solitary kidney takes on more significant prognostic and therapeutic importance.
Duplex ultrasonographic scanning combines a B-mode ultrasonographic image with a pulse Doppler unit to obtain flow velocity data. The technique is noninvasive, relatively inexpensive, and can be used in patients with any level of renal function. The test is very sensitive and specific (98%); however, it is very labor intensive and technician-dependent. Thus, duplex ultrasonographic scanning may not be available in many medical centers.
Radermacher et al reported that the renal resistance index, calculated through the use of color Doppler ultrasonography, can be used to predict the outcome of invasive therapy for renal artery stenosis.Patients with a resistance index (calculated as [1 - end-diastolic velocity divided by maximal systolic velocity] x 100) greater than 80, indicating small vessel and large vessel disease, were likely to have a poor response to angioplasty or surgery with respect to improvement in hypertension, renal function, or kidney survival. [21]
Radionuclide scanning
Use of radionuclide scanning, particularly following a single dose of captopril, is more useful in patients with normal renal function, in whom fibromuscular disease is suspected. See the image below.
Renal artery stenosis/renovascular hypertension. Left, Sonograms of the kidneys on a 57-year-old woman with difficult-to-control hypertension shows kidneys of uneven sizes: The left kidney is 96 mm, and the right kidney is 63 mm. Top right, Isotopic renogram (obtained with technetium mercaptoacetyltriglycine [MAG3]) after captopril shows a markedly depressed renal function in the right kidney. Bottom right, Analogous images show negligible activity in the right kidney. Note that this pattern is more typical for DTPA than MAG3 (as DTPA depends on the glomerular filtration rate for uptake which is decreased after captopril in renovascular hypertension [RVHT]). In severe cases of RVHT, MAG3 uptake can be decreased, as in this case. However, typically, uptake is preserved with decreased cortical excretion.
Stratigis et al reported that captopril renal scintigraphy was highly accurate in predicting the clinical outcome of percutaneous renal revascularization with stenting in patients with atherosclerotic renal artery stenosis who have a high coronary artery disease burden. In their study of 64 consecutive patients referred after coronary angiography, scintigraphy had sensitivity and specificity of 100% for both a hypertension and renal benefit from renal revascularization in patients with atherosclerotic renal artery stenosis of ≥ 70%. [22]
Patients with possible ischemic nephropathy (ie, serum creatinine values >2 mg/dL) frequently have associated parenchymal disease or bilateral vascular disease, in which case, the results obtained with scanning are unable to distinguish between parenchymal renal disease and renal artery stenosis/ischemic nephropathy.
Spiral CT angiography
This technique involves the use of an intravenous injection of a relatively large dose of iodinated contrast material and allows 3-dimensional reconstruction images of the renal arteries.
In 1995, Olbricht et al compared renal CT angiography with arterial digital subtraction angiography for detecting renal artery narrowing of more than 50%. [23] The CT technique showed positive and negative predictive values of 91%.
Spiral CT angiography is a useful technique that avoids arterial catheterization and produces accurate images of renal artery anatomy. This technique requires iodinated contrast material and significant time to perform the computer-based reconstruction. This technique avoids arterial puncture and, thus, the risk of atheroemboli, but it can be associated with contrast associated nephropathy, particularly in patients with preexisting chronic kidney disease.
Magnetic resonance imaging
Magnetic resonance angiography (MRA) is a noninvasive technique capable of demonstrating the renal vascular anatomy and revealing physiological information about kidney function (see the image below). This technique is capable of direct visualization of renal artery lesions without iodinated contrast material and provides a measurement of the absolute blood flow rate, GFR, and renal perfusion rate. Furthermore, MRA can provide accurate serial renal size and volume measurement. The limitations of MRA are its expense and its contraindication in patients with metallic clips, pacemakers, intraocular metallic devices, or other implants.
Three-dimensional gadolinium-enhanced magnetic resonance angiograms (MRAs) show medial fibroplasia, which appears as classic string-of-beads sign. This sign is due to multiple stenoses with intervening outpouchings that form a chain. In this case, the lesions involve the main right renal artery and the right accessory renal artery in a 37-year-old man with difficult-to-control hypertension.
Concern regarding the association of gadolinium use with the development of nephrogenic systemic fibrosis (NSF) in patients with moderate to severe renal insufficiency significantly limits the use of this agent and, therefore, this modality, for the recognition of anatomic renal artery stenosis. In one study, for example, Broome et al reported an odds ratio of 22.3 for the development of NSF in dialysis patients who underwent enhanced imaging with the gadolinium-based contrast agent gadodiamide (vs patients in the study who underwent unenhanced imaging). [24]
However, all of the patients in the Broome study who developed NSF received 0.2 mmol/kg of gadodiamide; no cases of NSF were found among members of the cohort who received 0.1 mmol/kg of the agent. In a subsequent study, Garovic et al found no reported cases of NSF among 335 patients who underwent contrast-enhanced MRA, using 0.1 mmol/kg gadodiamide, for suspected or known renal artery stenosis. [25]
MRA has been validated only for the stenosis situated in the proximal 3-3.5 cm of renal arteries. Distal renal artery stenosis and segmental renal artery stenosis were generally not analyzed. The sensitivity of MRA was 90% for proximal renal artery stenosis, 82% for main renal artery stenosis, and 0% for segmental stenosis. In a follow-up study, Loubeyre and colleagues examined 46 patients with clinical renal artery stenosis. [26] Using a combination of techniques, they determined a sensitivity of 100%, a specificity of 90%, a positive predictive value of 58%, and a negative predictive value of 100% for detecting stenosis of the main, but not accessory or distal, renal artery. These data were obtained with fast-scanning machines using gadolinium enhancement and a breath-holding technique. [27]
An additional study compared the accuracy of CT angiography and MRA to digital subtraction angiography and concluded that digital subtraction angiography remains the method of choice to establish a diagnosis.
However, in the above-mentioned study by Garovic et al, the diagnostic efficacy of contrast-enhanced MRA (using 0.1 mmol/kg gadodiamide) was compared with that of intra-arterial digital subtraction angiography, using a cohort of 335 patients with known or suspected renal artery stenosis. The authors concluded, based on image analyses by multiple readers, that the sensitivity and specificity of the 2 modalities were equivalent in the evaluation of renal artery stenosis. [25]
Blood oxygen level–dependent MRI
Blood oxygen level–dependent (BOLD) MRI is a noninvasive technique for evaluating kidney tissue oxygenation that requires no contrast exposure and has the potential to allow functional assessment for patients with atherosclerotic renal artery stenosis. Although a decrease in renal blood flow does not invariably lead to renal hypoxia, severe vascular occlusion can overwhelm the kidney's capacity to adapt to reduced blood flow, and BOLD MRI has demonstrated renal cortical hypoxia in patients with severe renal artery stenosis. [28]
Conventional arteriography
This technique remains the criterion standard for the confirmation and identification of renal artery occlusion in persons with IRD. Specialists can perform renal arteriography by conventional aortography, intravenous subtraction angiography, intra-arterial subtraction angiography, or carbon dioxide angiography. See the images below.
Renal artery stenosis/renovascular hypertension. Left, Flush aortogram in a 63-year-old man with hypertension shows marked stenosis of the right renal artery and complete occlusion of the left renal artery. Note the extensive atheroma in the aorta and iliac arteries. Right, nephrogram-phase image shows a significantly smaller left kidney with a faint nephrogram. Some blood supply to the left kidney is retained via collaterals (see image on the left).
Conventional flush aortogram in a 47-year-old woman with difficult-to-control hypertension shows the characteristic string-of-beads sign (arrows) of the right renal artery due to medial fibroplasia.
Conventional aortography produces excellent radiographic images of the renal artery, but it requires an arterial puncture, carries the risk of cholesterol emboli, and uses a moderate amount of contrast material with the risk of contrast-induced acute tubular necrosis (ATN). Low osmolar contrast material can limit the risk of this complication. Complication rates for renal angiography are 6-10% in most series.
Intravenous subtraction angiography is sensitive for identifying stenosis of the main renal artery but does not demonstrate accessory or branch renal arteries sufficiently. Solitary stenosis of a branch of the renal artery is a common source of renovascular hypertension in pediatric patients, among the fraction in whom the disorder does not result from syndromes such as neurofibromatosis. [29] However, intravenous subtraction angiography avoids the use of a high volume of contrast and the risk of artery puncture and arterial atherosclerotic emboli.
Intra-arterial digital subtraction angiography has a high diagnostic accuracy compared to conventional angiography and is associated with fewer complications, lower doses of contrast, and smaller catheter size.
Carbon dioxide angiography is an alternative angiographic contrast agent used in combination with digital subtraction angiography to avoid the risk of conventional nephrotoxic contrast agents in patients with severe renal insufficiency. The images obtained are similar in quality to intra-arterial digital subtraction angiography; however, the technique requires an experienced investigator and a dedicated person to inject the carbon dioxide. Discomfort and inadequate images are potential complications of the procedure.
Contrast nephrotoxicity
Patients with progressive ischemic nephropathy (ie, underlying chronic renal failure) are at risk for contrast nephrotoxicity and should be informed of this risk prior to any contrast procedure.
Contrast nephropathy typically manifests as a brief rise in the serum creatinine level 3-6 days after exposure to radiocontrast and is reported in up to 40% of patients with underlying renal failure.
Most patients with contrast nephropathy ultimately recover renal function. Porter reviewed results from nearly 300 patients with contrast nephropathy and concluded that fewer than 10% of these patients required dialysis permanently.
Selection of diagnostic tests
Once patients are identified as being at high risk for renal artery stenosis, the choice of the best test for diagnosis is controversial.
Accurate identification of patients with correctable renovascular hypertension can be difficult with use of standard noninvasive techniques (eg, sonography) because they provide only indirect evidence of the presence of renal artery lesions.
On the other hand, invasive techniques with more accurate diagnostic potential can produce a worsening of renal function because of contrast toxicity and complications related to the procedures themselves (eg, arterial puncture, catheter-induced atheroembolism).
Gilfeather et al performed a study evaluating conventional angiography versus gadolinium-enhanced MRA in 54 patients and 107 kidneys. [30] The study showed that in 70 kidneys (65%), the average degree of stenosis reported by readers of both modalities differed by 10% or less. In 22 cases (21%), MRA overestimated the degree of stenosis by more than 10% relative to the results of conventional angiography; in 15 cases (14%), MRA underestimated the stenosis by more than 10%.
The obvious advantages of conventional angiography are its ability to determine the clinical importance of suggestive lesions and the ability to concurrently perform endovascular therapy. In addition, measurement of the pressure gradient across a stenotic lesion may be helpful in determining the clinical significance of a lesion. [31] However, specialists should weigh these advantages against the higher cost and greater morbidity of conventional angiography. The slightly inferior variability of MRA in diagnostic interpretation further supports the use of this technique as potentially the most appropriate tool for screening patients strongly suggested to have atherosclerotic RVD.
See Imaging in Renal Artery Stenosis/Renovascular Hypertension for a complete discussion of this topic.
Incidental atherosclerotic renovascular disease is often discovered in patients at the time of cardiac angiography. The impact of this finding on a patient’s outcome and, therefore, on the need to dilate and stent the renal vessel, the so-called "drive-by" percutaneous transluminal renal angioplasty with stenting (PTRAS), is the subject of intense debate. [32, 33, 34]
-
Renal artery stenosis/renovascular hypertension. Left, Sonograms of the kidneys on a 57-year-old woman with difficult-to-control hypertension shows kidneys of uneven sizes: The left kidney is 96 mm, and the right kidney is 63 mm. Top right, Isotopic renogram (obtained with technetium mercaptoacetyltriglycine [MAG3]) after captopril shows a markedly depressed renal function in the right kidney. Bottom right, Analogous images show negligible activity in the right kidney. Note that this pattern is more typical for DTPA than MAG3 (as DTPA depends on the glomerular filtration rate for uptake which is decreased after captopril in renovascular hypertension [RVHT]). In severe cases of RVHT, MAG3 uptake can be decreased, as in this case. However, typically, uptake is preserved with decreased cortical excretion.
-
Renal artery stenosis/renovascular hypertension. Left, Flush aortogram in a 63-year-old man with hypertension shows marked stenosis of the right renal artery and complete occlusion of the left renal artery. Note the extensive atheroma in the aorta and iliac arteries. Right, nephrogram-phase image shows a significantly smaller left kidney with a faint nephrogram. Some blood supply to the left kidney is retained via collaterals (see image on the left).
-
Renal artery stenosis/renovascular hypertension. Flush aortogram in a 32-year-old man with familial hypercholesterolemia and difficult-to-control hypertension. Radiograph shows a complete occlusion of the right renal artery and marked stenosis of the left renal artery (arrow).
-
Three-dimensional gadolinium-enhanced magnetic resonance angiograms (MRAs) show medial fibroplasia, which appears as classic string-of-beads sign. This sign is due to multiple stenoses with intervening outpouchings that form a chain. In this case, the lesions involve the main right renal artery and the right accessory renal artery in a 37-year-old man with difficult-to-control hypertension.
-
Conventional flush aortogram in a 47-year-old woman with difficult-to-control hypertension shows the characteristic string-of-beads sign (arrows) of the right renal artery due to medial fibroplasia.
