ABSTRACT: Purpose. To evaluate the feasibility and safety of renal artery angioplasty and stenting utilizing a distal protection device to reduce the risk of intraprocedural atheroembolism. Methods. Twenty-eight hypertensive patients (18 men; mean age 71.3 ± 8.6 years, range 49–87) with atherosclerotic renal artery stenosis (4 bilateral) underwent angioplasty and stenting with distal protection in 32 renal arteries (29 ostial lesions). The lesion was crossed with a GuardWire temporary occlusion balloon, which was inflated to provide parenchymal protection. Generated debris was aspirated and analyzed. Blood pressure and serum creatinine levels were followed. Results. Immediate technical success was 100%. All lesions were stented, either directly (14 ostial lesions), after predilation (15 ostial lesions), or owing to suboptimal angioplasty (3 nonostial lesions). Visible debris was aspirated from all patients. Mean particle number and diameter were 98.1 ± 60.0 per procedure (range 13–208) and 201.2 ± 76.0 mm (range 38–6206), respectively. Mean renal artery occlusion time was 6.55 ± 2.46 minutes (range 2.29–13.21). Mean follow-up was 6.7 ± 2.9 months (range 2–17). Systolic and diastolic blood pressure declined from 167.0 ± 15.2 and 103.0 ± 12.0 mmHg, respectively, to 154.7 ± 12.3 and 93.2 ± 6.8 mmHg after the procedure. The mean creatinine level dropped from 1.34 ± 0.35 mg/dL preprocedurally to 1.22 ± 0.36 mg/dL at 24 hours and remained constant. At 6-month follow-up, renal function did not deteriorate in any patient, whereas 5 patients with baseline renal insufficiency improved after the procedure. Conclusions. These preliminary results suggest the feasibility and safety of distal balloon occlusion during renal interventions to protect against atheroembolism. This technique’s beneficial effects should be evaluated by randomized studies. J Endovasc Ther 2001;8:227–237 Keywords: atheroembolism, atherosclerosis, balloon angioplasty, hypertension, renal stenosis Endovascular treatment of atherosclerotic renal artery stenosis (RAS) is now a well-accepted alternative for revascularization.1,2 This method has been proposed as the standard of care for nonostial renal artery lesions, and although initial studies concerning the treatment of ostial lesions yielded varying results,3,4 recent series suggest that vascular endoprostheses are highly effective in the ostial segment.5–9 However, postprocedural deterioration of renal function occurs in a subset of patients after percutaneous renal angioplasty.10–12 Atheroembolism during the procedure has been implicated as a precipitating factor for this complication.13–15 In order to eliminate the risk of atheroembolic material being carried into the renal parenchyma, we applied a novel technique consisting of balloon angioplasty and stenting with distal balloon protection followed by debris aspiration, a concept currently being evaluated in carotid artery angioplasty.16 Methods Patient characteristics. From January 1999 to June 2000, 28 patients with hypertension (18 men; mean age 71.3 ± 8.6 years) who were diagnosed with atherosclerotic RAS by renal duplex scanning and digital subtraction arteriography were treated with percutaneous angioplasty and stenting under distal embolic protection. Because of the currently available dimensions of the protection balloon, patients with renal artery diameter > 6 mm were excluded from this study, as were patients with bifurcated or trifurcated renal arteries in which the lesion was positioned = 2.0 mg/dL). Four patients had bilateral disease. The renal artery stenosis was located at the ostium in 29 (91%) cases. Mean diameter stenosis was 81.6% ± 8.5% (range 70–95%). Mean lesion length was 12.1 ± 3.9 mm (range 10–29). The diameter of the artery was estimated at 6 mm in 21 cases and 5 mm in 11 cases. Nineteen (68%) patients had diffuse, severe atherosclerosis of the abdominal aorta. Five (18%) patients had diabetes mellitus; 20 (71%) were current smokers, and 14 (50%) had hyperlipidemia. Sixteen (57%) patients had associated coronary artery disease; cerebrovascular disease was found in 8 (29%) and peripheral arterial disease in 14 (50%). Device description. The GuardWire System (PercuSurge Inc. Sunnyvale, California) consists of 3 components: 1. The GuardWire temporary occlusion catheter is a 0.014- or 0.018-inch hollowtube angioplasty wire made of nitinol. Incorporated into its distal segment is an inflatable, compliant elastomeric balloon with a radiopaque marker. The diameter of the balloon (5 or 6 mm) is chosen depending on the diameter of the artery. The distal 3.5 cm of the wire is floppy and shapeable. The wire is available in lengths of 190 and 300 cm, allowing monorail or over-the-wire techniques for angioplasty and stenting. 2. The proximal end of the hypotube wire incorporates a Microseal device that keeps the elastomeric balloon inflated to protect the kidney from atheroembolism during intraluminal maneuvers and at the same time allows catheter exchange at the proximal end, similar to commonly used guidewires. 3. The 5.2 French (Fr) Export aspiration catheter is placed over the shaft of the GuardWire prior to distal balloon deflation to aspirate the debris through a 1-mm sidehole. This catheter is tapered to the guidewire to avoid the risk of debris generation or stent dislodgment during its advancement into the renal artery. Protected angioplasty/stenting technique. All procedures were performed under local anesthesia and intravenous sedation. An intravenous bolus of 5,000 units of unfractionated heparin and 3 mg of cefamandole nitrate were routinely administered at the beginning of the procedure. An 8 Fr guiding catheter was placed at the ostium of the renal artery via a percutaneous femoral approach. In cases of high-grade lesions or those with acute angles between the aorta and the renal artery, a coaxial technique with a 5 Fr Simmons-type selective catheter placed inside the guiding catheter was used to catheterize the renal artery. The lesion was then crossed with a coronary 0.014-inch wire. The guiding catheter was slowly advanced at the renal ostium over the Simmons catheter, and then the coronary wire and the Simmons catheter were both removed. In a little more than half of the cases, predilation with a 4- to 5-mm balloon was necessary to facilitate advancing the guiding catheter into the renal artery without dislodgment of debris. In the remaining cases, direct stenting without predilation was chosen because the guiding catheter could easily slide over the Simmons catheter. With the guiding catheter appropriately positioned, the GuardWire was carefully advanced across the lesion (Figure 1A), and the marker of the protection balloon was placed 2 or 3 cm beyond the target site. The Microseal adapter was attached and the occlusion balloon inflated to occlude the renal artery (Figure 1B). On detaching the adapter, the occlusion balloon remained inflated. For ostial lesions, which were routinely stented, care was taken to position the stent so that it would protrude slightly into the aortic lumen; 1 to 2 mm. The proximal part of the stent was redilated with a balloon 1 mm larger in diameter. Four different stent models were used with no particular selection criteria applied: Palmaz (Cordis Endovascular, Warren, New Jersey), AVE (Medtronic AVE, Santa Rosa, California), Herculink (Guidant Corporation, Santa Clara, California), and Corinthian (Cordis Endovascular). After stent deployment (Figure 1C), the aspiration catheter was advanced over the wire to the level of the lesion and positioned adjacent to the protection balloon (Figure 1D). Any debris was removed using a 20-mL syringe connected to the proximal end of this catheter. After removing the aspiration catheter, the Microseal adapter was reattached to the Guard Wire, and the occlusion balloon was deflated, allowing normal vessel flow (Figure 1E). If the angiographic result was satisfactory, the device was removed. To facilitate balloon withdrawal and prevent it from getting caught on the stent, the guiding catheter was routinely advanced into the stent up to its distal end. The aspirated blood was sent to the laboratory for analysis. The postprocedural drug regimen included aspirin (100 mg/d) indefinitely and ticlopidine (250 to 500 mg/day) or clopidogrel (75 mg/day) for 1 month. Patients remained in the hospital for 48 hours to monitor serum creatinine levels and adjust blood pressure medications. Renal duplex scanning was scheduled at 6 and 12 months and then annually; angiography was performed at 6 months or when restenosis was suspected on the basis of positive clinical and duplex scan findings. Serum creatinine values were measured before and after the procedure (day 1) and at 1 and 6 months, with biannual measurements thereafter. Definitions and statistical analyses. Ostial lesions were defined as stenoses > 50% occurring within 5 mm of the aortic lumen as assessed by arteriography.9 Immediate technical success was defined as residual stenosis, 30% of the reference diameter (measured by quantitative angiographic analysis) without significant periprocedural complications. Inability to successfully place the GuardWire at the correct position to protect the kidney throughout the procedure was considered to be failure of the device. Duplex criteria for restenosis were a loss of the early systolic notch and a systolic velocity > 1.5 m/s. The angiographic criterion for restenosis was the development of luminal narrowing > 50% of the reference diameter. Reversal of hypertension was defined as diastolic blood pressure 17 Moderate renal insufficiency was defined as baseline serum creatinine from 1.5 to 1.9 mg/dL; a value >= 2.0 mg/dL was categorized as severe insufficiency.9,18 A decrease .0.2 mg/dL from the preprocedural creatinine values represented an improvement, whereas values within ± 0.2 mg/dL of baseline were considered unchanged. An increase > 0.2 mg/dL was considered as deterioration in renal function.18 Determination of vessel diameter was made by sizing the guiding catheter against the normal vessel distal to the lesion using quantitative analysis. Continuous data are presented as mean ± SD and categorical data as percentages. Statistical differences between groups were determined by the Student t test. Statistical significance was taken at p Particulate analysis. The aspirated blood samples from all patients were analyzed and studied by microscopy and scanning electron microscopy (Figure 4). Different particles were isolated and identified. Their number varied from 13 to 208 per procedure (mean 98.1 ± 60.0), and diameter ranged from 38 to 6206 mm (mean 201.2 ± 76.2 mm). Excluding one 6.2-mm fragment, the mean particle diameter was 188.0 ± 49.8 mm. In cases of direct stenting, the average number of extracted particles per procedure was 112.0 ± 73.5. When predilation of the lesion was performed, the mean particle number was 86.0 ± 47.0 (p = 0.36). Also, we did not notice a significant statistical difference between the mean diameters of the particles after direct stenting versus after predilation (190.0 ± 44.5 mm versus 210.0 ± 96.0 mm, respectively, p = 0.56). For the 3 nonostial lesions, aspiration was performed both after angioplasty and after stenting, and more particles were collected with the second aspiration (64 versus 80). The particles were atheromatous plaques, cholesterol crystals, necrotic cores, fibrin, thrombi, platelets, and macrophage foam cells. Follow-up. The mean follow-up period was 6.7 ± 2.9 months (range 2–17); in all cases, follow-up was beyond the period required for development of clinical manifestations of atheroembolism. One patient who underwent coronary angioplasty before renal stenting died 3 days after the procedure from myocardial infarction. One patient developed bilateral restenosis (6.3%) at 6 months; these lesions were treated successfully with repeat dilation. No deterioration of renal function was observed in any patient. The mean creatinine value was 1.34 ± 0.35 mg/dL preprocedurally, 1.22 ± 0.36 mg/dL at 24 hours, 1.35 ± 0.43 mg/dL at 1 month, and 1.24 ± 0.30 mg/dL at 6 months (20 patients). Five (18%) patients with baseline renal insufficiency had improvement at 6 months after the procedure. As regards the effects of the procedure on hypertension, 4 (14.3%) patients were cured, 15 (53.6%) improved, and 9 (32.1%) remained unchanged. Systolic blood pressure dropped from 167.0 ± 15.2 to 154.7 ± 12.3 mmHg in this group of patients. The mean reduction in systolic blood pressure was 12.3 ± 9.5 mmHg (range 7.4–17.3, p = 0.001). Diastolic blood pressure dropped from 103.0 ± 12.0 to 93.2 ± 6.8 mmHg after the procedure; mean reduction in diastolic blood pressure was 10.3 ± 8.6 mmHg (range 5.9–14.7, p = 0.001). The number of medications also declined from 2.2 ± 0.8 to 1.2 ± 0.7 per patient (1.0 ± 0.7 mean reduction per patient). Discussion In recent years, percutaneous angioplasty techniques have become the cornerstone of the therapeutic strategy for addressing renal artery stenosis. The goals of endovascular management are normalization or at least an improvement in the control of blood pressure and stabilization or improvement of renal function. Recent studies regarding the effects of angioplasty or stenting on renal function show that a large percentage of patients seem to benefit from the procedure.8–11,18–21 However, in many of these series, a decline in renal function was noted in a subset of patients even after successful initial technical results. In a prospective study, Dorros et al.10 used primary stent placement for atherosclerotic renal artery stenosis in 76 patients. The 6-month follow-up showed that serum creatinine values improved in 30%, were unchanged in 48%, and deteriorated in 22% of the patients. In a later study18 of 141 patients with 6-month follow-up, they reported that renal function stabilized or improved in the two thirds of unilateral stenosis patients, whereas one third had an increase in creatinine by > 0.2 mg/dL above baseline. Lack of complete angiographic follow-up limited their understanding of the worsening renal function in patients with normal baseline creatinine after successful revascularization. Recently, Isles et al.11 published a review of 10 studies, examining 416 stent placement procedures in 379 patients treated for renal artery stenosis. Although technical success was high in all studies (96–100%), renal function improved in 26%, stabilized in 48%, and deteriorated in 26% of the patients. Many factors may account for this functional deterioration: contrast media-induced nephrotoxicity, progression of concomitant nephrosclerosis, restenosis of the renal artery, and atheroembolism during the procedure.10 Notably, the majority of these factors are iatrogenic in origin.22 Consequently, proper patient selection, application of strict indications for intervention, meticulous techniques, and adequate follow-up are of paramount importance. Although considerable efforts have been directed toward more effective and safer endovascular procedures for renal artery stenosis, little attention has been given to the detrimental effects of atheroembolism on renal function. This entity is caused by the release of microscopic plaque fragments and cholesterol crystals from the renal artery lesion or the atherosclerotic aorta into parenchymal renal vasculature during the procedure.22–25 Instrument manipulation in the aorta and renal arteries can result in detachment and embolism of atheromatous debris from ulcerated plaques. The large size of the devices used, an increased length, or specific difficulties of the procedure may be contributory. There is also evidence that both oral and intravenous anticoagulants and thrombolytic drugs can induce atheroembolism.26,27 The true incidence of atheroembolism is uncertain because many patients can have a silent course because of the large functional kidney reserve, which allows normal serum creatinine values despite a significant decline in total glomerular filtration. Therefore, only the most severe cases may be detected, especially in patients with preprocedural renal dysfunction and limited functional reserve. Clinical manifestations of the disease are nonspecific as well. Thadhani et al.28 retrospectively evaluated 52 patients with both renal failure and histologically proven atheroembolism after angiography or cardiovascular surgery over a 10-year period. Within 30 days of their procedure, 50% of patients had cutaneous signs of atheroembolism and 14% had documented blood eosinophilia. Most patients reach a peak serum creatinine level over 3 to 8 weeks,29 but onset is usually sooner.12 Although proteinuria and nephrotic syndrome are uncommon, Haqqie et al.29 reported 4 patients with histopathologically documented atheroembolism who developed nephrotic-range proteinuria. They suggested that atheroembolism should be considered in the differential diagnosis of nephrotic syndrome in elderly patients with serious vascular disease. Similar conclusions were made by Greenberg et al.30 after reviewing the clinical features and histological findings of 24 patients found to have cholesterol atheroembolism at renal biopsy; 19 had recently undergone an invasive vascular procedure. Even in cases with high clinical suspicion, the diagnosis of atheroembolism is difficult to establish using routine laboratory tests. Renal biopsy is the only definitive diagnostic tool; although it is valuable to exclude other potentially treatable disease processes, its routine application for confirmation of a disease amenable only to supportive treatment is problematic. For these reasons, it is not surprising that atheroembolism after renal artery interventions is often misdiagnosed as drug-induced nephrotoxicity or the progression of nephrosclerosis. Few studies have addressed the problem of atheroembolism after renal artery interventions, but, interestingly, it was the predominant complication in all of them. Boisclair et al.12 published their results of successful stent placement in 33 patients either for immediate angioplasty failure or recurrent stenosis. Seven patients developed complications, including 4 with renal artery emboli. In another study, van de Ven et al.13 reported that after successful stenting in 24 patients with an atherosclerotic ostial renal artery stenosis, 2 developed renal insufficiency due to cholesterol embolism. Also, Wilms et al.15 observed 2 cases of renal deterioration, including a case of massive cholesterol embolism, among 11 patients with stent-supported renal angioplasty. Renal atheroembolism definitely poses a risk of renal function deterioration and decreased survival in patients undergoing endovascular procedures for renal artery stenosis. Due to the increasing number of such patients, the cost of renal function deterioration and subsequent end-stage renal disease requiring dialysis represents a significant long-term problem. Its importance is clearly demonstrated in a recent work by Krishnamurthi et al.,31 who evaluated its impact on survival in 44 patients who had surgery for atherosclerotic RAS and concomitant intraoperative renal biopsy for detection of atheroemboli. Atheroembolic disease was identified in the biopsy specimens in 16 (36%) patients and correlated significantly with decreased survival (54% 5-year survival in this group versus 85% in patients without atheroembolism, p = 0.011). To avoid atheroembolic events during renal interventions, the procedure should be as atraumatic as possible, with use of small devices and adaptation of coronary angioplasty techniques. Recently, Feldman et al.,32 recognizing the risk of atheroembolism, reported their ‘‘no-touch’’ technique, which consists of placing a second 0.035-inch J-wire within the guiding catheter during cannulation of the renal artery to prevent the tip of the catheter from rubbing the aortic wall in an effort to minimize its contact with atherosclerotic plaques and reduce the potential for embolization. Beyond these technical considerations to circumvent atheroembolism, we applied the concept of protected renal angioplasty and stenting. The rationale for distal embolic protection is similar to that of brain protection during angioplasty of the carotid arteries. This technique, based on the pioneering work of Théron,33 is being evaluated by many groups to prevent stroke. We postulated that the same technique could be suitable in the management of renal artery stenosis, mitigating the risk of atheroembolism. Our results show stabilization or improvement of renal function with no deterioration. This may well be attributed to the use of the protection system during the intervention. It is noteworthy that visible atherosclerotic debris was extracted in all cases. In 1 instance, we removed a fragment measuring 6.2 mm in its maximum diameter, large enough to produce macroembolism or even renal artery occlusion. In our experience, protected renal angioplasty and stenting seems to have the same effect on hypertension as performing the procedures without protection7: significant decreases in systolic and diastolic blood pressure, easier blood pressure control, and reduced antihypertensive medications. Larger randomized studies are needed to confirm this observation. Moreover, the absence of renal deterioration after protected renal angioplasty and stenting could influence the longterm prognosis of hypertension, and further studies are needed to appreciate the impact of unchanged renal function on hypertension. Although no device-related complications occurred in this small series of patients, adding another instrument to the procedure while trying to prevent complications could create new problems. The potential for renal artery thrombosis during protection balloon inflation and flow occlusion is negligible, because the patients are under heparin and antiplatelet therapy; moreover, the duration of occlusion is usually short, less than the time required to perform the distal anastomosis of a conventional aortorenal bypass. The predetermined volume needed to fully inflate the balloon and its compliant nature should obviate renal artery dissection. There could also be a potential increased risk for distal atheroembolism when this technique is used if the generated debris were directed into the lower extremities. To reduce the likelihood of this complication, debris was removed by aspiration alone; flushing of the treated area was not performed. Inability to deflate the protection balloon after stenting is a possible, but rare, scenario. We faced this complication once with the same device during our ongoing study of protected carotid interventions. It was easily managed by cutting the GuardWire distal to the Microseal adapter segment. Also, the interventionist should remember that this technique does not protect the kidney from atheroembolism during attempts to initially catheterize the renal artery and cross the lesion. Finally, the additional cost of the protection device must be balanced with its potential benefit. This study raises a number of questions that remain unanswered. Is this technique indicated for all patients undergoing endovascular treatment for renal artery stenosis, or should it be limited to those with pronounced aortic atherosclerosis, baseline renal insufficiency, and/or ostial renal artery lesions? Is there any role for intravascular ultrasound in this arena? In this study, we demonstrated the feasibility and safety of balloon-protected renal angioplasty and stenting in the prevention of renal atheroembolism in a small cohort. Larger randomized trials will be needed to definitively address the utility of this approach and better document its beneficial effect on renal function and, perhaps, on hypertension and its long-term prognosis.
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