Introduction
A key principle governing renal artery stenting (RAS) is that clinical benefit will result from relieving a significant renal artery stenosis causing renal hypoperfusion. Published meta-analyses suggest that a very high RAS technical success rate (>95%) is accompanied by a surprisingly modest and inconsistent clinical improvement ( Figure 20-1 ). The discordance between the high technical success rate for RAS and the inconsistent clinical response suggests the following:
- 1.
Successful RAS procedures were performed on nonobstructive RAS (stenoses not causing symptomatic renal hypoperfusion).
- 2.
That the clinical syndrome being treated (hypertension or renal insufficiency) was not caused by renal hypoperfusion.
Diagnosis
Screening for Renal Artery Stenosis
Screening for renal artery stenosis is appropriate in patients at increased risk for this disease ( Table 20-1 ). Whenever possible, screening tests for renal artery stenosis should be performed noninvasively using direct imaging tests such as Doppler ultrasound, computed tomographic angiography (CTA), or magnetic resonance angiography (MRA). Noninvasive imaging has become so sophisticated and accurate that it is seldom necessary to perform catheter-based angiography for the diagnosis of renal artery disease.
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The appropriateness of screening angiography for RAS at the time of cardiac or peripheral vascular angiography of other vascular beds has been addressed by recommendations and guidelines endorsed by an expert consensus panel of the American College of Cardiology (ACC) and the American Heart Association (AHA). For patients with risk factors as outlined in Table 20-1 or clinical syndromes suggestive of RAS, aortography is given a Class I indication for screening at the time of angiography performed for other clinical indications. There is published evidence that nonselective, diagnostic, screening renal angiography is safe and is not associated with any incremental risk when performed at the time of cardiac catheterization.
Duplex Ultrasonography
Duplex ultrasonography (DUS) is an excellent test to detect renal artery stenosis but is highly dependent upon the skills of the technician performing the test. It is the least expensive of the imaging modalities and provides useful information about the degree of stenosis, the kidney size and other associated disease processes such as obstruction. The location and degree of stenosis can accurately be determined by duplex ultrasound of the renal artery.
Overall, when compared with angiography, DUS has a sensitivity and specificity of 84% to 98% and 62% to 99%, respectively, when used to diagnose renal artery stenosis. Renal artery duplex is an excellent test for the follow-up of RAS after revascularization. Following endovascular therapy a renal artery duplex should be obtained within the first few weeks to establish a baseline, at 6 months, 12 months, and yearly thereafter.
One drawback of DUS is that the sensitivity is lower for identifying accessory renal arteries (67%) compared with main renal arteries (98%). Therefore, if the patient has hypertension that cannot be adequately controlled with a good regimen, and the DUS fails to demonstrate RAS, another imaging modality may be considered to identify stenosis of an accessory renal artery.
Detecting renal artery in-stent restenosis (ISR) is a potential problem when native vessel parameters are used for diagnosis. Recently a cohort of 132 patients with renal artery stents had angiographic correlation with DUS findings. There was no single peak systolic velocity (PSV) cutoff that would accurately discriminate 60% to 99% from 0% to 59% restenosis in all patients. A PSV <241 cm/s was useful in excluding ISR (negative predictive value 96%): 78 of 81 renal arteries with PSV <241 cm/s had 0% to 59% restenosis. A PSV ≥296 cm/s was accurate in predicting ISR (positive predictive value 94%): 33 of 35 renal arteries with a PSV ≥296 cm/s had ISR by angiography. A PSV between 241 and 295 cm/s represented an indeterminate zone in which renal artery restenosis could not be diagnosed or excluded on the basis of DUS alone.
Resistive Index
The resistive index (RI) is obtained by measuring the peak systolic velocity (PSV) and the end diastolic velocity within the renal parenchyma at the level of the cortical blood vessels. It is an indication of the amount of small vessel arterial disease (i.e., nephrosclerosis) within the renal parenchyma. The renal artery RI has inappropriately been suggested as a method to stratify patients likely to respond to renal intervention. However, a prospective study of renal stent placement by Zeller et al. demonstrated that an elevated RI predicted a favorable blood pressure response and renal functional improvement at 1 year after renal arterial intervention. If there are good clinical reasons to revascularize a kidney, then it should be performed independently of the RI.
Noninvasive Angiography
Computed tomographic angiography (CTA) uses ionizing radiation and iodinated contrast to produce excellent images of the abdominal vasculature ( Figure 20-2 ). CTA has a sensitivity and specificity for detecting RAS of 89% to 100% and specificity of 82% to 100%. Excellent three-dimensional image quality with enhanced resolution can be obtained with multidetector-row CTA technology. The advantages of CTA over magnetic resonance angiography (MRA) includes higher spatial resolution, absence of flow-related phenomena that may overestimate the degree of stenosis, and the capability to visualize calcification and metallic implants such as endovascular stents and stent grafts. CTA is generally well tolerated with an open gantry and thus claustrophobia is not as limiting a factor as it is for MRA. The disadvantages of CTA compared with MRA are exposure to ionizing radiation and the need to administer potentially nephrotoxic iodinated contrast agents.
MRA also provides excellent imaging of the abdominal vasculature and associated anatomical structures. When compared with angiography, MRA has demonstrated a sensitivity of 91% to 100% and a specificity of 71% to 100%. Contrast-enhanced MRA using gadolinium improves image quality when compared with noncontrast studies and shortens imaging time, thereby eliminating some of the artifact created by gross patient movement. However, MRA does not have the same sensitivity and specificity in patients with fibromuscular dysplasia (FMD) and is generally not a good screening test if FMD is suspected.
MRA should not be used in patients with a glomerular filtration rate less than 30 mL/min/1.73 m 2 because of the increased likelihood of developing nephrogenic systemic sclerosis. MRA may not be used in patients with metallic (ferromagnetic) implants such as some mechanical heart valves, cerebral aneurysm clips, and electrically activated implants (pacemakers, spinal cord stimulators). At the present time, MRA is not useful in following patients after stent implantation due to artifact produced by the metallic stent.
Invasive Angiography
The “Achilles’ heel” of renal stenting is the inaccuracy of the angiographic determination of the severity of renal stenoses. The traditional “gold” standard for determining the severity of renal artery stenosis has been invasive angiography. Even with quantitative measurement, angiography may be unable to discriminate between nonobstructive stenoses and clinically significant ones ( Figure 20-3 ). Most would agree that interventionalists are able to identify “critical” stenoses in renal arteries, but for mild to moderately severe lesions, physiological confirmation is necessary.
Translesional Pressure Gradients
Confirmation of the correlation with hemodynamic evidence of significant renal artery stenosis and renin release has been documented by De Bruyne and colleagues. Other investigators have now established that hemodynamic parameters of significant renal artery stenosis (peak systolic gradient >21 mm Hg, renal fractional flow reserve of ≤0.8, and a dopamine-induced mean translesional gradient ≥20 mm Hg) are associated with clinical improvement after renal stenting in patients with mild to moderate renal artery stenoses.
TIMI Frame Count
Angiographic measurements of renal blood flow by using renal frame counts (RFC) and renal blush grades (RBG) for microvascular flow can differentiate normal patients from patients with FMD. Hypertensive patients with renal artery stenoses have also been shown to have decreased renal perfusion as measured by RFC. Clinical responders tended to have higher baseline RFCs than nonresponders and had greater improvement in their RFC values following RAS. Three-quarters of the hypertensive patients who responded to RAS had a baseline RFC ≥25, and if the RFC improved by >4, then 79% were responders to RAS.
Renal Artery Intervention
The pathophysiology of renovascular hypertension has been well understood since the experiments of Goldblatt and others. Modern confirmation of this cause and effect relationship was demonstrated by DeBruyne and colleagues, who performed an in vivo experiment that showed a threshold gradient (Pd/Pa ≤0.9) for the release of renin following graded renal artery obstruction. Much confusion was brought to the field by the early introduction of percutaneous balloon angioplasty as a very successful treatment for renal artery FMD, but it suffered a moderately high failure rate for atherosclerotic renal artery stenosis. The over-estimation of the success rate for atherosclerotic lesions led to underpowered clinical trials, making it very difficult to demonstrate successful treatment outcomes. Balloon angioplasty was subsequently shown to be inferior to renal stenting in atherosclerotic renal artery stenosis.
Renal artery restenosis after stent placement is related to both acute gain and late loss, similar to coronary artery restenosis. Quantitative angiography on a series of 100 consecutive patients was carried out and found that patients with patent renal arteries had significantly larger renal stent minimal lumen diameters (MLD) (4.3 ± 0.7 mm vs. 4.9 ± 0.9 mm; p = 0.025), and had significantly less late loss (1.3 ± 0.9 mm vs. 3.0 ± 1.4 mm; p < 0.001). In the largest single series of renal stent implantation, a larger reference vessel diameter (RVD), and larger acute gain (i.e., poststent MLD) after stent deployment were strongly associated with a lower incidence of restenosis. For example, restenosis in a vessel with an RVD of <4.5 mm was 36% compared with only 6.5% for an artery with an RVD of >6.0 mm in diameter. Renal stenting has been shown to be a durable treatment with 1-year patency rates ≥85% ( Table 20-2 ) and 5-year primary patency approaching 80%.
| AUTHOR | ARTERIES TREATED (n) | RESTENOSIS RATE (%) |
|---|---|---|
| Blum et al. | 74 | 11.0 |
| Tuttle et al. | 148 | 14.0 |
| Henry et al. | 209 | 11.4 |
| Van de Ven et al. | 43 | 14.0 |
| Rocha-Singh et al. | 180 | 12.0 |
Percutaneous catheter-based therapy with primary stent placement has replaced open surgery as the treatment of choice for atherosclerotic renal artery stenosis ( and ). However, despite a technical success rate exceeding 95% for renal artery stent placement, there remains wide variation in the reported success rates in improving hypertension. While at least some of the variability in outcomes is attributable to a lack of standard reporting criteria, the dominant factor appears to be poor patient and lesion selection for treatment. Variability in the angiographic assessment of the hemodynamic severity of renal artery stenoses has undermined the predictability of a treatment response with success stenting. While the majority of hypertensive patients with atherosclerotic renal artery stenosis and hypertension will experience improved blood pressure control and/or the need for fewer medications, very few patients will be cured of hypertension (see Figure 20-1 ).
Technique for Renal Artery Intervention
Aspirin is started at least one day prior to the procedure, while the use of dual antiplatelet therapy is at the discretion of the operator, but not supported by any evidence base. Retrograde femoral access is most commonly chosen, although radial artery access is rapidly gaining acceptance (see further on). For retrograde common femoral artery access, a 6 Fr or 7 Fr sheath is placed and 3000 to 5000 U of unfractionated heparin are given to achieve a target activated clotting time (ACT) of approximately 250 seconds. A 4 Fr diagnostic catheter (internal mammary or Judkins right coronary shape) is placed through a 6 Fr “short” (50-60 cm) angled (hockey-stick or renal shaped) guiding catheter, to engage the ostium of the renal artery. A 0.014-inch coronary angioplasty guidewire is advanced across the lesion, and the guide catheter is then telescoped (advanced) over the 4 Fr diagnostic catheter, allowing the larger catheter to atraumatically engage the renal artery ostium.
A second technique for safely engaging the atherosclerotic renal ostium is the “no touch” technique. A 0.035-inch J-guidewire is advanced into the descending thoracic aorta above the renal arteries. The renal guide catheter is advanced over the J-wire until it is near the renal ostium. By gently manipulating (advancing and/or withdrawing) the 0.035-inch J-wire in the aorta, the tip of the guide catheter can be steered nearer to the renal artery ostium. When the guide is near the renal artery ostium, a 0.014-inch steerable guidewire is advanced through the guide catheter (alongside the 0.035-inch wire) and exiting the guide catheter near the ostium to enter into the renal artery and cross the stenosis into the distal portion of the renal artery. As the 0.035-inch guidewire is withdrawn, the guide catheter will atraumatically engage the renal ostium over the 0.014-inch wire.
A balloon sized 1:1 with the reference vessel diameter is inflated using the lowest pressure that will fully expand the balloon. This ensures that the calcified renal artery stenosis is dilatable, and also helps to choose the stent size. If the patient experiences discomfort during balloon inflation, the inflation should be terminated and the patient, lesion, and sizing reassessed. Pain may be due to stretching of the adventitial layers of the vessel and may be a precursor to arterial rupture or dissection. Balloon expandable stents, long enough to cover the lesion and sized 1:1 with the reference diameter, are used to scaffold the lesion and maximize the angiographic result.
Renal Artery Atherosclerotic Lesions
Atherosclerotic renal artery stenosis usually involves the ostial and very proximal portion of the main renal artery. These lesions are morphologically complex and can be difficult to visualize with two-dimensional angiography. The errors made with angiography are increased when interventionalists rely on “visual estimation” as the only means to determine lesion severity. Under the best of circumstances, visual estimation of angiographic stenoses lacks reproducibility and precision. Confirmation of the hemodynamic significance of the renal artery stenosis is encouraged. Balloon angioplasty is associated with a lower success rate for atherosclerotic lesions, with a restenosis rate of approximately 50% over 6 months. Aorto-ostial renal artery lesions are particularly difficult to effectively treat with balloon dilation alone. They are especially prone to restenosis due to vascular recoil caused by confluent plaque from the wall of the aorta extending into the ostium of the renal artery and are considered by many experts as unsuitable lesions for balloon angioplasty alone.
A strategy of primary renal artery stent placement has replaced provisional (bail-out) stent placement. A randomized controlled trial clearly demonstrated superiority of renal stents over balloons alone in atherosclerotic renal artery stenoses for procedure success, late patency, and cost-effectiveness.
Atheroemboli are a concern with atherosclerotic lesions. Henry and coworkers placed renal stents in 65 renal arteries in 56 patients using emboli protection devices (EPDs). They noted debris retrieval following renal stent deployment in 100% of the patients with distal balloon occlusion (Percusurge (n = 38), Medtronic, Minnesota), and in 80% of the filter cases (FilterWire (n = 26), BSC, Natick, Massachusetts) and (Angioguard (n = 1), Cordis, Miami, Florida). Interestingly, there was no difference in the size or number of particles regardless of whether balloon predilation was performed or not. With the reported frequency of visible atherosclerotic debris recovered with EPDs well above 50%, it is not surprising that 25% of successfully revascularized kidneys show a decline in renal function.
Fibromuscular Dysplasia
Fibromuscular dysplasia (FMD) is commonly found in young adults, especially women, but the condition can persist into later life. The angiographic appearance of a corrugated vessel is diagnostic of FMD. In a patient with FMD who is hypertensive despite maximal medical therapy, balloon angioplasty alone is indicated and the patient will usually respond to balloon angioplasty without the need for stenting. Balloon angioplasty is the treatment of choice for renal artery stenoses caused by FMD. If the patient fails to respond to balloon angioplasty alone, or restenosis occurs, then renal stenting is a reasonable option.
Procedural Complications
Complications associated with catheter-based renal intervention are related to vascular access, catheter trauma, or systemic complications related to contrast reactions or renal toxicity. Vascular access complications are the most common complication in renal artery intervention. They include access site bleeding and hematoma (1.5% to 5%), access site vessel injury (1% to 2%), retroperitoneal hematoma (<1%), pseudoaneurysm (0.5% to 1%), arteriovenous fistula, and nerve injury (<1%). Major complications of peripheral vascular angiography range from 1.9% to 2.9% ( Table 20-3 ).
| AUTHOR | PATIENTS (n) | DEATH (%) | DIALYSIS (%) | MAJOR COMPLICATIONS (%) |
|---|---|---|---|---|
| Tuttle et al. | 148 | 0 | 0 | 4.1 |
| Rocha-Singh et al. | 180 | 0.6 | 0 | 2.6 |
| Burket et al. | 171 | 0 | 0.7 | 0.7 |
| White et al. | 133 | 0 | 0 | 0.75 |
| Dorros et al. | 163 | 0.6 | 0 | 1.8 |
| TOTAL/MEAN | 795 | <1.0 | <1.0 | 2.0 |
Catheter-related renal artery complications include atheroembolism, vessel dissection, or arterial perforation, which are rare (<1%) but often devastating events. Anaphylactoid contrast reactions occur in fewer than 3% of cases, and less than 1% require hospitalization. The risk of contrast-induced nephropathy (CIN) is increased in patients with baseline chronic renal insufficiency, diabetes mellitus, multiple myeloma, and those who are receiving other nephrotoxic drugs such as aminoglycosides. Prevention of CIN requires vigorous hydration and the use of as little iso-osmolar contrast as possible.
Embolus Protection Devices
Embolus protection devices (EPDs) have been developed for clinical use in saphenous vein coronary bypass grafts and for cerebral protection during carotid stent placement. EPDs are percutaneous devices that can be divided into three categories as follows:
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filters
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dista locclusion balloons with aspiration of debris
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proximal occlusion balloons with reversal of flow
The aorto-ostial nature of most renal artery stenoses makes proximal occlusion devices unsuitable, which is why distal occlusion balloons and filters are the most common devices used in an off-label manner for renal protection.
In a single small randomized study of 100 patients that compared four arms, these were:
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control
- •
EPD
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IIb/IIIa antagonist
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EPD + IIb/IIIa inhibitor
The control group, EPD group, and IIb/IIIa antagonist group demonstrated a decline in glomerular filtration rate (p < 0.05), but group 4 (combination therapy with EPD + IIb/IIIa antagonist), did not decline and was superior to the other groups (p < 0.01). The main effects of treatment demonstrated no overall improvement in glomerular filtration rate; although abciximab was superior to placebo (0 ± 27% vs. −10 ± 20%; p < 0.05), embolic protection was not (−1 ± 28% vs. −10 ± 20%; p < 0.08). An interaction was observed between abciximab and embolic protection (p < 0.05), favoring combination treatment. Abciximab reduced the occurrence of platelet-rich emboli in the filters from 42% to 7% (p < 0.01).
Radial Artery Access
Vascular access complications account for the majority of clinical complications of renal stenting. One way to minimize access site bleeding is to use the radial artery. The coronary interventional literature has demonstrated a marked reduction in vascular access complications with radial artery access compared with both brachial and femoral artery access. Low profile radial sheaths and the ability to use a “sheathless” technique with 6 Fr guiding catheters make the radial artery approach a viable option ( Figure 20-4 ). In addition to minimizing vascular access complications, the radial artery approach has other advantages including increased patient acceptance and improved guiding catheter engagement due to the downward or caudal orientation of most renal arteries. The radial approach requires 125-cm guide catheters with 150-cm shaft length balloons and stents and there is a minor learning curve. The undeniable benefit of the radial access approach, however, is a major reduction in the vascular access related complications with same day discharge and increased patient satisfaction.
