Renal artery stenosis has been recognized as an important cause of progressive renal insufficiency1 that is believed to account for refractory hypertension in about 1% of hypertensive patients.2 Accurate information regarding the pathological and morphological characteristics of the renal artery stenosis is essential for treatment planning.

Digital subtraction angiography (DSA) is currently the standard diagnosis method for the detection and quantification of renal arterial stenosis. The invasive nature of this technique and its 2D perspective limitations, however, have prompted investigators to apply duplex ultrasonography,3,4 CT angiography,5,6 and 3D gadolinium-enhanced MR angiography7,8 as well. All of these are considered reliable screening tools, based on their high accuracy in the detection of renal artery stenosis. Duplex ultrasound examinations of the renal arteries, however, are highly operator-dependent and sometimes yield inadequate results due to bowel gas or obesity. CT angiography is an ionizing exam that requires up to 120 mL of contrast material for adequate opacification of the renal arteries, which may increase the risk of inducing nephrotoxicity.

MRA has therefore emerged as the preferred technique in patients with poor renal function or allergy to iodinated contrast material and patients in whom DSA cannot be performed.9 MRA has been found superior to duplex ultrasound in detecting renal artery stenosis.10 In addition, postprocessing renal MRA by using a volume rendering algorithm enhances its diagnostic accuracy and overcomes several known limitations of the maximum intensity projection algorithm (Figure 1).11

Morphologically, renal artery stenosis is categorized as ostial (within 5 mm of the aortic lumen caused by extension of aortic bulky plaques into the origin of the renal artery), proximal (5 to 10 mm from the aortic lumen with an aortic cuff), or truncal (more than 10 mm distal to the aortic lumen).12 Pathologically, the most common renal artery lesion in patients over the age of 50 is atherosclerosis, while fibromuscular hyperplasia is more common in patients under the age of 40. Clinically, renal artery stenosis may result in accelerated and/or poorly controlled hypertension with or without deterioration of renal function and recurrent pulmonary edema. Many patients who are found to have renal artery stenoses do not have either of these clinical situations, however.13

Natural history studies have shown that progression of atherosclerotic renal artery stenosis is relatively common, with an average rate of 7% per year.14 Therefore, a stenotic renal arterial lesion necessitates intervention when it causes clinical symptoms or shows significant hemodynamic effects and, thus, increased risk of developing to an occlusion and losing renal function. The degree of stenosis that causes significant hemodynamic effects was indicated in several studies to be greater than 50%,15,16 60%,13,17 or greater than 70%.1,18-20 At our institution, we consider that stenoses greater than 70% represent the critical stenosis level that reduces the blood flow and poststenotic perfusion pressure during reductions in systemic arterial pressure (Figure 2). Silent renal artery stenoses are followed up clinically by means of recurrent blood pressure and serum creatinine measurements as well as radiologically by using duplex ultrasound, MR angiography, or CT angiography.

ANGIOPLASTY AND STENTING

In 1978, percutaneous transluminal renal angioplasty (PTRA) was introduced by Gruntzig et al21 as an alternative to surgical treatment for renal artery stenosis. Its beneficial effect on blood pressure control, nondeleterious effect on renal function, and long-term patency have brought PTRA wide acceptance in treating truncal and proximal renal artery stenosis. In contrast, PTRA of atherosclerotic ostial renal artery stenosis has acknowledged limitations inferred from an elastic recoil rate that varies between 9% and 76%22,23 and a late restenosis rate that varies between 25% and 45%.24,25 Anatomic and pathologic aspects of this critical type of renal artery stenosis, estimated to represent 11% to 40% of atherosclerotic renovascular lesions,12 are believed to be responsible for the disappointing results of the procedure.18 Stent placement has been applied to overcome the limitations of acute and late failure of balloon angioplasty.15,26,27

Stent deployment may be primary or secondary after an unsuccessful PTRA via a femoral or less common brachial approach. Primary stenting is usually performed after a predilation of the stenotic lesion: An undersized angioplasty balloon is used to decrease the inflation pressure required for stent expansion28 and to ensure that full expansion of the lesion is possible.29 To prevent the stent from migrating after deployment, the stent is overdilated up to 0.5 to 1 mm larger than the original artery. Overdilation of the stent would help, in addition, to compensate for the neointimal growth observed after stent placement.30 In the management of atherosclerotic ostial renal artery stenosis, van de Ven et al16 found in their randomized trial that primary stenting would be more efficient than trying PTRA as the first procedure. Before proceeding to dilation of the stenosis, a 5000-IU bolus of heparin calcium is injected intra-arterially as a prophylactic procedure against thrombosis during the intervention.

The criteria for successful angioplasty or stent placement, as assessed by repeated angiography and determination of the transstenotic pressure gradients, include treatment of the stenosis with a residual stenosis less than 20% and a transstenotic systolic pressure gradient less than 10 mm Hg and insertion of the stent at the desired position. Although this definition is inconsistent between published studies, it is important to substantially improve the renal arterial lumen after stenting because the final diameter after intervention has been found to be an important indicator of the risk of restenosis.29

The immediate technical success rate of PTRA for the treatment of truncal and proximal renal artery stenoses is excellent, but for ostial stenosis, it ranges from 24% to 91%.16 Stent revascularization has greatly improved the initial technical success rate, which ranges from 72% to 100%.16,31

In our institution, 62 patients (25 women and 37 men with an age range of 49 to 91 and a mean age of 68 plus/minus 10 years) with atherosclerotic ostial renal artery stenosis were treated with stent placement between April 1996 and March 2000. Treatment followed an unsuccessful PTRA in 39 patients (47 arteries) and was primary in 23 patients (25 arteries). All stenotic lesions but one were treated with one stent, and adequate coverage of the stenosis was achieved at the first attempt in 71 of 72 arteries. Therefore, initial technical success was achieved in 98.6% of stent placement procedures. In one case, the stent was dislocated distally into the renal artery during selective catheterization to obtain postprocedural blood pressure gradient. This dislocation resulted in an insufficient coverage of the ostial stenosis and was managed with a second overlapping stent in the ostial segment of the artery.

COMPLICATIONS

Complications that may occur during the intervention are related either to the catheterization procedure or to angioplasty and stent placement. The former include arterial dissection, guidewire perforation of the kidney, femoral pseudoaneurysm, and groin hematoma. The latter include stent misplacement or dislodgment and acute thrombosis of the stent.32 Severe complications may occur after the intervention, including renal failure, segmental renal infarction, proteinuria, and cholesterol embolism.

After intervention, patients are required to undergo continual follow-up examinations that monitor blood pressure, drug therapy, and serum creatinine in addition to radiological assessment of stent patency. Follow-up studies are attempted at six months after intervention and at yearly intervals.

Because clinical features such as hypertension and renal function deterioration, unfortunately, do not always indicate a restenosis, radiological follow-up of stented renal arteries is essential for early detection of recurring diminished blood flow due to in-stent stenosis. Reported radiological follow-up results are most commonly based on angiographic findings.16,17,28 Although the gold standard intra-arterial DSA allows for measurement of transstenotic blood pressure gradients, the invasive nature of DSA prevents its routine use for follow-up.

Duplex ultrasonography12,15,33,34 has been used to evaluate renal arterial stent patency. Duplex ultrasound examinations of the renal arteries are operator-dependent, however, and sometimes yield inadequate results due to bowel gas, obesity, and/or failure to obtain a Doppler signal within the stent.35 Although MR angiography is useful for the follow-up of patients treated with PTRA (Figure 3), it is adversely affected by stent-related susceptibility artifacts. In vitro, Wallstents and Palmaz stents have been found to cause large signal voids on MRA, making assessment of the stent lumen impossible.36 In one study,37 phased-contrast MRA was used in two stented renal arteries to investigate the presence of a hemodynamic restenosis by measuring the flow velocity beyond the stent. This trial resulted in one false-positive restenosis.

The application of CT angiography to follow up stented renal arteries remains limited, although a number of studies describe the technique.17,38 In our experience, multislice CTA is a useful noninvasive technique to follow up patients treated with a renal artery stent. CT angiograms allowed for a complete evaluation of the arterial lumen from the aorta to the segmental renal arteries and a comprehensive assessment of the patency of the deployed stent. The stent lumen is clearly evaluated with adequate image quality and lumen delineation on axial as well as coronal images (Mallouhi et al, presented at Radiological Society of North America meeting 2000). Particularly useful is the postprocessing of multislice CTA data sets with volume rendering (VR). The use of subvolume VR images allows the opportunity to display a direct image of the stent lumen without the necessity of eliminating overlaying structures or undergoing time-consuming image segmentation. In addition, the color coding of different attenuating materials in the histogram enables good delineation of the stent lumen (Figure 4).

The assessment of stent patency in our patient population is performed by means of duplex ultrasound and, since August 1999, by multislice CTA. Intra-arterial DSA is performed when a significant restenosis is suspected on the basis of clinical findings, duplex ultrasound, or CTA.

RESTENOSIS

On DSA, a narrowing of greater than or equal to 50% of stent lumen and/or a transstenotic manometric gradient of greater than or equal to 20 mm Hg indicates a significant restenosis. In addition, a peak systolic velocity of 226 cm/sec or more35 with duplex ultrasound or a reduction of 50% or more in stent lumen with CTA is considered an indication of a significant restenosis.

Renal arteries treated with PTRA may develop a restenosis in up to 55% of the cases. After stent placement, a restenosis may develop in up to 39%. Leertour et al31 found in their meta-analysis that restenosis rates after stent placement were significantly lower than those after PTRA alone.

The mean follow-up period for our study group was 24.8 plus/minus 13.7 months (range, five to 55 months). Eight stents were followed up for 48 months, 15 for 36 months, 37 for 24 months, and 60 for 12 months. Eight substantial restenoses (greater than or equal to 50%) and one chronic occlusion developed in seven patients (12.5%) at a mean time of 20 plus/minus 14 (range, three to 36 months) after intervention; four patients had recurrent hypertension; and a fifth patient showed unchanged hypertension. The chronic occlusion occurred together with a severe contralateral restenosis in a patient with bilateral renal stenting. This patient was lost for 24 months during follow-up, and stent occlusion resulted in a nonfunctional kidney.

Hemodynamically significant renal artery restenosis may cause recurrence of hypertension and/or deterioration of renal function, and it must be treated. After unsuccessful primary PTRA, a stent could be placed across the stenosis. In case of in-stent stenosis, re-PTRA is performed or a second stent could be deployed.

CLINICAL RESULTS

Blood pressure response is evaluated by continuous observations of systolic and diastolic pressures before and after stent placement. The clinical effect of renal arterial intervention on blood pressure is expressed in terms of cure, improvement, or no change. Cure of hypertension corresponded to a diastolic blood pressure of 90 mm Hg or less and/or a systolic pressure of 160 mm Hg or less while the patient needed no antihypertensive medication. Improvement corresponds to a decrease in diastolic pressure of 15% or more, or a decrease of systolic pressure of 10% or more while the patient is taking the same or fewer antihypertensive medications. If otherwise, hypertension is considered not changed.

Several studies have shown that the percentage of patients in whom hypertension improved as a result of PTRA and stent placement was significantly higher than that of patients cured or with unchanged hypertension.31 Other studies indicated that mean systolic and diastolic blood pressures decreased significantly after PTRA or stent placement in comparison with the baseline pre-procedure.12 Hypertension is more likely to be cured after revascularization in patients with fibromuscular dysplasia than in those with atherosclerotic renal artery stenosis (60% vs. <30%), regardless of the type of revascularization.39

Renal function response is considered improved when the serum creatinine values decrease more than 0.2 mg/dL, stabilized when the change is within plus/minus 0.2 mg/dL, and deteriorated when values increase more than 0.2 mg/dL. After revascularization, renal function improves in 40% to 55% of patients and deteriorates further in 14% to 30%.39 Renal function in patients in whom it was impaired (>1.5 mg/dL) was improved in 30% and stabilized in 38%.29 A baseline serum creatinine concentration of more than 1.5 mg/dL, however, was the strongest independent predictor of late death.40

Figures 5 and 6 show the clinical results of our patient population. According to the criteria previously described, hypertension was cured in two (3%) patients (including one patient with a restenosis), improved in 53 (86%) patients, and did not change in seven (11%) patients.

A slight increase in mean serum creatinine level during follow-up was observed in comparison with that before stent placement in patients with normal renal function at the baseline (mean SC increased from 1.03 plus/minus 0.19 mg/dL to 1.15 plus/minus 0.36 mg/dL; p=0.003) as well as in patients with preexisting renal function impairment (mean SC increased from 2.24 plus/minus 0.94 mg/dL to 2.34 plus/minus 1.21 mg/dL; p=0.758). On the basis of a 0.2 mg/dL change in serum creatinine level, renal function improved in eight (13%) patients, stabilized in 40 (65%), and deteriorated in 14 (22%).

For the evaluation of patients with clinical findings suggestive of renal artery stenosis or restenosis after PTRA, renal MRA could be performed as the first-line diagnostic examination. Multislice CTA is a useful noninvasive technique for the follow-up of patients treated with renal artery stenting.

Percutaneous revascularization of hemodynamically stenotic renal arteries has been established as an effective treatment procedure to maintain renal blood flow and restore adequate perfusion pressure with high initial success and low complication rates. Consequently, PTRA and stent placement have apparent effects on improving blood pressure and stabilizing renal function.

DR. MALLOUHI and DR. CZERMAK are radiologists, Dr. Waldenberger is head of interventional radiology, DR. JASCHKE is chair of radiology, and DR. SEILER is a resident doctor in vascular surgery, all at the Leopold-Franzens University in Innsbruck, Austria.

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