Renal Artery Stenting With Embolic Protection
Embolic protection during renal stenting may be beneficial, but new device designs are necessary.
Renal artery stenosis (RAS) is the most common cause of secondary hypertension, with an estimated incidence of 5% in the hypertensive population. Atherosclerosis is by far the most common cause of RAS. Atherosclerosis affecting the renal artery is a progressive disease that most often results from encroachment of aortic plaque into the renal ostium.1-3 Endovascular management of RAS is the primary modality of treatment with a very high success rate, low complication rate, and acceptable long-term patency. Nonetheless, renal artery percutaneous treatment is not universally accepted as safe and effective. This lack of acceptance mainly stems from postprocedural temporal deterioration of renal function and variable long-term improvement in blood pressure control in this patient population.4-6 Postprocedural deterioration in renal function may occur in 20% to 40% of cases7,8 and is an important limitation of this technique.
Deterioration in renal function may occur either due to deleterious effects of contrast media or atheroembolization during percutaneous intervention. Like many other vascular beds, such as the carotids, saphenous vein grafts, and certain coronary lesions, atheroembolization may occur during any renal artery intervention. Most patients undergoing renal endovascular revascularization have clinically silent renal atheroembolization. Patients with baseline renal insufficiency or poor functional reserve may have clinical expression of renal atheroembolization. Although it is logical that embolic protection devices are needed during renal artery intervention, very limited data exist in the literature to support its use. Moreover, many technical and device design issues are unresolved.
In this article, two cases of renal artery intervention performed with embolic protection will be discussed.
The patient was an 80-year-old man who had coronary artery disease, hypertension, diabetes, and chronic obstructive pulmonary disease. He underwent cardiac catheterization after an episode of angina and congestive heart failure in January 2005. At that time, an abdominal aortogram demonstrated severe atheromatous disease of the distal abdominal aorta, with severe bilateral renal artery stenoses. At that time, his creatinine value was 0.9 mg/dL, and his hypertension was medically controlled. During the next 6 months, blood pressure control diminished despite three antihypertensive medications, and his creatinine value increased to 1.2 mg/dL. The patient was referred for revascularization of his renal arteries. Because of the severe aortic disease and baseline mild renal insufficiency with bilateral disease, the interventional plan consisted of renal artery stenting with embolic protection.
An 8-F renal diagnostic RDC(I) (Cordis Endovascular, a Johnson & Johnson company, Miami, FL) guiding catheter was used with extreme care to engage the left renal artery ostium. A translesion pressure gradient was not measured to prevent excess manipulation at the ostium and potential risk of embolization. Intravenous bivalirudin was used as an anticoagulant. After measuring the diameter of the landing zone, a FilterWire EZ was deployed. The artery was then stented with a 7-mm X 15-mm Genesis (Cordis) stent with an excellent angiographic result (Figure 1 A-C). The same guide catheter was then placed in the ostium of the right renal artery. The right renal artery contained early bifurcation. An angiogram showed that the upper branch appeared to provide blood supply to the larger portion of renal parenchyma. There was insufficient space for FilterWire placement before the bifurcation. Therefore, a FilterWire was deployed in the upper branch to provide partial protection (Figures 2 and 3). The ostium was then stented with a 6.5-mm X 18-mm Genesis stent with no residual stenosis. The patient was kept in the hospital for 48 hours for blood pressure monitoring and evaluation of renal function. His blood pressure exhibited minor improvement and renal function was stable. The patient was re-evaluated 1 week after the procedure and, at that time, his blood pressure medications were decreased from three to two. Three weeks later, his renal function remained stable and blood pressure control was considered optimal.
The patient was a 76-year-old woman with severe hypertension, coronary artery disease, peripheral vascular disease, and mild aortic stenosis. Despite four antihypertensive medications, her systolic pressure remained above 200 mm Hg. She underwent a renal artery duplex scan, which showed a proximal left renal artery velocity of 255 cm/s, with a renal/aortic ratio of 4.9 and a resistive index of 0.19, suggesting severe stenosis. She was referred for left renal artery intervention. An abdominal aortogram (Figures 4 and 5) showed severe atheromatous plaque encroachment of the left renal artery ostium. A 6-F RDC(I) guide catheter (Cordis) was used to engage the left renal artery. Intravenous bivalirudin was utilized for anticoagulation. A 5-mm Angioguard RX short tip embolic protection device (Cordis Endovascular, Investigational Device, not approved for use in US) was deployed in the main renal artery
(Figure 6). The left renal artery ostial lesion was primarily stented with a 5.5-mm X 18-mm Genesis stent (Figures 7 and 8). The patient’s baseline creatinine level was
1.5 mg/dL; at follow-up 2 weeks after the procedure, it was 0.9 mg/dL. The systolic blood pressure at follow-up was 150 mm Hg, with three antihypertensive medications.
There is much evidence that atheroembolization occurs in many vascular interventions, especially during carotid artery and saphenous vein graft stenting procedures. During the last few years, several prospective randomized clinical trials and registry studies have demonstrated the short-term and long-term benefit of embolic protection in association with these procedures.
Similarly, atheroembolization is probably a clinical or subclinical complication of renal artery intervention. Deterioration in renal function after the procedure may occur due to contrast-induced nephrotoxicity, progression of concomitant nephrosclerosis, restenosis and, most importantly, atheroembolism.9 The importance of careful patient selection, appropriate guide catheter and guidewire selection, and meticulous technique cannot be stressed enough. An ex vivo study by Rapp et al demonstrated that a large number of atherosclerotic fragments are released during renal intervention.10 These fragments are of sufficient size to create vascular occlusion and ischemic renal parenchymal damage. During this experiment, every step of the procedure—including wire passage, balloon angioplasty, and stent placement—was associated with the release of embolic debris. This ex vivo study used an .018-inch guidewire,
3-mm to 5-mm balloons, and 5-mm or 6-mm stents—an assortment of devices similar to those used for renal artery intervention.
Walker et al have also demonstrated the high potential for embolic debris during placement of guide catheters, sheaths, or diagnostic catheters. They performed an aggressive aspiration of these catheters and discovered large (1-mm to 3-mm) particles in 41.7% of patients.11 This led to the adaptation of the “no-touch” technique described by Feldman et al.12
Isles et al published reviews of 10 studies examining a total of 416 stent placement procedures in 379 patients treated for RAS. Technical success was high, ranging from 96% to 100%. Despite the high technical success rate, 26% of patients had deterioration in renal function.13 Similarly, in a study published by Dorros et al in which primary stenting was utilized in 76 patients, 22% had deterioration of renal function.9
DIAGNOSING THE DISEASE
The diagnosis of renal atheroembolism is problematic, and the only definitive diagnostic test is renal biopsy, which is largely impractical for routine clinical practice. Moreover, the true incidence of renal atheroembolism is hard to predict because only patients with baseline renal insufficiency and poor functional reserve may express clinical characteristics suggestive of atheroembolism.
Clinical manifestations of the disease are nonspecific as well. Thadani et al retrospectively examined 52 patients with both renal failure and histologically proven atheroembolism after angiography or cardiovascular surgery.14 Within a month after their procedure, 50% of the patients had cutaneous signs of atheroembolism, and 14% had eosinophils on the peripheral blood smear. The serum creatinine level peaked in most patients within 3 to 8 weeks, but onset was usually earlier.2 Nephrotic range proteinuria and nephrotic syndrome are uncommon but have been reported in association with renal atheroembolization.15
Krishnamurthi et al evaluated the impact of renal artery atheroembolism on survival rate. In this study, 44 patients underwent surgery for atherosclerotic RAS and concomitant renal biopsy. Thirty-six percent of patients had biopsy evidence of atheroembolism. The 5-year survival in these patients was only 54% compared to 85% in patients without atheroembolism.16
Renal impairment after atheroembolism ranges from modest deterioration to severe renal failure requiring dialysis. Abrupt onset of renal failure may occur, although more frequently progressive loss of renal function over 3 to 8 weeks leads to late deterioration. Moreover, atheroembolism cases are frequently misdiagnosed as dye-induced nephrotoxicity, which generally occurs 1 to 2 days after the procedure and often resolves within a few days or weeks.
Much effort has been made to perfect the technique of renal artery stenting, including the development of specific guide catheters and sheaths, renal specific wires, low-profile balloons, and stent delivery systems. However, little attention has been paid to prevention of atheroembolism. This is largely due to the unavailability of renal-specific embolic protection devices. Moreover, no randomized control data exist on the use of embolic protection devices in renal intervention. Henry et al performed renal intervention with protection devices in a small group of patients using balloon occlusion as well as filter protection devices.17-20 Although the number of patients treated was small, this experience has aided our understanding of the potential utility and efficacy of embolic protection devices in this intervention. Because of the limitations of available protection devices, arteries larger than 6 mm in size were too large for the balloon occlusion device (GuardWire, Medtronic, Santa Rosa, CA). Arteries larger than 5.5 mm in size were excluded for use of the FilterWire. The Angioguard filter, which is available up to 8 mm, was used only in three cases. Forty-five patients were treated using the GuardWire, and 52 patients underwent renal artery stenting with FilterWire embolic protection.
Serum creatinine levels were measured before and after the procedure at 1 day, 1 month, 6 months, and biannually thereafter. Reported mean follow-up was 14.2±5 months (2 to 66 months). There was no acute deterioration in renal function. At 6 months, 74 patients were in the study, and only one patient showed deterioration (1.3%), whereas 17 patients showed improved renal function. At 2 years, 54 patients remained in the study and, at 3 years, 29 patients were available for long-term follow-up. At 3-year follow-up, 93% of the patients (n=27) had either stable or improved renal function. This was a substantial improvement when compared to historical reports of 20% to 40% of cases of renal function deterioration with nonprotected intervention. Holden et al performed 46 procedures in 37 patients with Angioguard filters.21 Their results were similar to Henry et al, with reported stable or improved renal function in 95% of cases. In the Holden series, 65% of the filters contained embolic debris.
In summary, early results of embolic protection device use during renal artery stenting are encouraging, but there are limitations.
Renal Artery-Specific Devices Need to Be Designed and Tested
Available embolic protection devices are not designed for use in the renal artery. First, several filter-based systems have a long radiopaque floppy tip guidewire that makes them undesirable in the renal bed. This may potentially cause damage in segmental arteries. Second, filter devices are relatively long and therefore are not compatible with the limited landing zone within the main renal artery. Third, the angulation that any of the current devices are required to take from the aorta to the renal artery may result in kinking of the retrieval catheter and, thus, an inability to retrieve the filter. Renal-specific retrieval catheters must be designed.
An ideal renal embolic protection device should be on a stiffer .014-inch or .018-inch wire with a short radiopaque tip, have a shorter landing zone requirement, be low-profile, and be available in a variety of diameters or have a range of expansion compatible with the target renal anatomy. Filter pore size and volume capacity should be addressed over time as more experience and data are obtained using current and future generations of devices. The advantages or disadvantages of balloon occlusion/aspiration devices and continuous flow filter devices within the renal indication remain to be resolved through comparative studies.
Renal Artery-Specific Issues
The early bifurcating renal artery poses a special problem. In the future, perhaps a proximal protection device could be developed to safeguard these patients. In case 1, a partial protection approach was utilized, but the clinical value of this technique is unclear. In addition, during renal interventions in the presence of other etiologies such as fibromuscular dysplasia, it is not clear whether embolic protection has a role. A National Heart and Lung Institute-sponsored trial (CORAL [Cardiovascular Outcomes in Renal Atherosclerotic Lesions]) is underway and utilizes one of the first renal-specific embolic protection devices (as in case 2). The results of the CORAL trial are years away, therefore what should clinicians do in the meantime to treat hypertensive patients with severe RAS? Intuitive knowledge of the embolic potential and single-center published reports demonstrating encouraging results after protected renal artery stenting, absence of renal-specific devices, and prospective randomized trial data make the use of embolic protection devices in renal artery intervention a clinical dilemma. In our clinical practice, patients with baseline renal insufficiency, a heavy atheromatous burden in the distal abdominal aorta, one functional kidney, or severe bilateral disease are offered a renal artery stent procedure with off-label embolic protection in suitable anatomy.
Rajesh M. Dave, MD, is Chairman of Endovascular Therapy at the Pinnacle Health Heart and Vascular Institute in Harrisburg, Pennsylvania. He has disclosed that he holds no financial interest in any product or manufacturer mentioned herein. Dr. Dave may be reached at (717) 920-4400; email@example.com.
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