Renal vascular interventions

Renal Vascu lar I n t e r v e n t i o n s

John H. Rundback and Joshua L. Weintraub

R ENAL ARTERY STENOSIS (RAS) secondary to atherosclerosis or fibromuscular dys-

plasia (FMD) is the most common origin of secondary hypertension. In young individuals, especially women, fibrodysplastic RAS has long been recognized as an infrequent but correctable cause of hypertension, in older patients, atherosclerotic (or atheromatous) RAS (ARAS), a man- ifestation of systemic atherosclerosis, is an increasingly recognized reason for renal insufficiency, t-3 As the median age of the United States population rises, 4 the prevalence of atherosclerotic RAS is increasing. This has resulted in recent dramatic increases in the use of renal artery angioplasty and stenting (Murphy T, personal communication)) Between 1996 and 2001, the annual volume of renal artery interventions billed to Medicare increased 242%, with an annual increase in renal artery stenting of 364%. Over the same time period, renal artery bypass surgery declined by 45% from 4,040 to 2,260 procedures annually, reflecting an increased trend toward percutaneous minimally invasive interventions for RAS (T Mur- phy, personal comanunication).

NATURAL HISTORY OF RAS

Atherosclerotic disease accounts for two thirds of cases of RAS. Approximately one third of lesions are bilateral, and 75% are ostial (variably defined but usually considered to be within 5 mm of the aortic lumen). As early as 1968, Meaney et al 5 and Wollenweber et al 6 in 2 separate reports noted that ARAS is often an anatomically progressive process. Meaney described interval worsening of ARAS in 36% of 39 patients followed for a mean 27 monthsfl whereas Wollenweber reported a somewhat higher 60% rate of disease progression in 30 patients followed for 28 months. More contemporary series have reproduced these earlier results. Becket et al 8 found that nearly 50% of lesions having a greater than 75% initial stenosis

From the New York Presbyterian Hospital, College of Phy- sicians and Surgeons of Columbia University, New York, NK

Address reprint requests to John H. Rundback, MD, FSIR, New York Presbyterian Hospital, New York, NY 10032.

Copyright 2002, Elsevier Science (USA). All rights reserved. 0037-198X/02/3704-0008535.00/0 do# l O.l O53/sroe.2002.35481

developed progressive stenosis or occlusion over a 13-month period. Tollefson and Ernst 9 performed sequential aortograms on 48 patients and found disease progression in 53%, with 7 arteries (all with initial stenosis >80%) developing occlusion. Schreiber and colleagues 1° reported a mean angiographic follow-up of 52 months on 85 patients with ARAS, with clinical follow-up out to 87 months. During that period of time, 44% of lesions progressed and 16% occluded. Progressive ARAS was associated with decreasing renal size and function but not with hypertension control. Finally, in a prospective study using renal duplex sonography over a mean of 32 months, Zierler et aP 1 found the cumulative incidence of ARAS progression from <60% to -->60% to be 48% at 3 years, with a cumulative rate of occlusion (for arteries initially greater then 60% stenosed) to be 7% at 3 years. Only 8% of patients with initially normal renal arteries developed a >60% stenosis during this same interval.

There has been limited data regarding the impact of ARAS on renal size and function. In their study, Wollenweber et al 6 described functional deterioration in 19%. Schreiber et allo noted decreasing renal size and function in 70% and 54% of their patients, respectively. In a 2-year follow-up of 54 patients with ARAS initially greater than 60%, Strandness ~2 reported an average decrease in renal length of 1.9 cm. The estimated risk of loss of more than 1 cm (approximately 30% of renal mass) was 19% at 1 year. In a retrospective evaluation of renal function deterioration, Connolly et a113 noted that the risk of eventual dialysis correlated with the initial angiographic pattern of disease. They found the 2-year, actuarial hemodialysis-free survival to be 97% for patients with unilateral stenosis, 82% for bilateral stenosis, and 45% with unilateral renal artery occlusion and contralateral stenosis or occlusion. ~3 In a prospective evaluation of renal function in patients with ARAS, Dean et a114 serially followed renal function in 41 patients over a range of 6 to 78 months. Forty-one percent eventually required surgical revascularization, either for progressive excretory dysfunction (present in 46%) or renal atrophy (>10% loss of renal length, present in 37%). Similar to other investigators, acceptable blood pressure control was noted in nearly all cases. Unfortunately, although

312 Seminars in Roentgenology, Vol 37, No 4 (October), 2002: pp 312-326

RENAL VASCULAR iNTERVENTIONS 313

Fig 1. Percutaneous transluminal renal angioplasty. A 43- year-old woman presented with new onset hypertension unre- sponsive to 3 medications. (A) Flush aortogram shows fibromuscular dysplasia (medial fibroplasia) involving the distal right renal artery. (B) Selective angiography shows the classic "string of beads" appearance. (C) Post-PTRA image shows marked improvement in the angiogram, The patient's hypertension resolved.

these data clearly suggest both anatomic and functional progression in many patients with atherosclerotic RAS, there remain no reliable predictors of disease progression on a case-to-case basis.

FMD consists of several histologic subtypes, with medial fibroplasia being the most common. This lesion is characterized by fibrous replacement of the vascular media resulting in alternating areas of arterial constriction and poststenotic dilatation, the classic "string of beads" appearance. Although almost one third of medial fibroplastic lesions will progress, occlusion is uncommon, and there generally is no change in renal size or function until late in the disease. ~5 Conversely, other forms of FMD, including perimedial fibroplasia and intimal hyperplasia, invariably result in progressive renal artery obstruction and renal atrophy. Although angiographic distinction of the different forms of FMD is important, all types respond well to percutaneous transluminal angioplasty, limiting the clinical importance of this differentiation (Fig 1).

PREVALENCE OF ARAS

In patients undergoing angiography for peripheral vascular disease (PVD), ARAS is present in 14% to 44% (Table 1)] 6-23 with bilateral disease present in approximately 20% to 29% of cases. 24-26 Among patients being evaluated for PVD, ARAS is more prevalent in patients with hypertension. Eyler et a116 evaluated the renal arteries in 500 patients undergoing peripheral angiography. In this series, ARAS was present in 62% of hypertensive patients compared with 32% of normotensive pa-

Table 1. Prevalence of RAS in Patients With PVD

Author Year n %RAS

Eyler et al TM 1962 500 44 Dustan et aH 7 1984 111 35 Bonomo et a118 1988 300 15 Priollet et a119 1990 99 14 Salmon and Brown 2° 1990 374 31 Choudri et a121 1990 100 42 Olin et a122 1990 395 44 Totals 1879 35

314 RUNDBACK AND WEINTRAUB

tients. ARAS has been similarly correlated with coronary and carotid atherosclerosis. 27,a8 Harding et a129 found significant ARAS in 15% of 1,235 patients undergoing cardiac catheterization, and Uzu et a125 discovered ARAS in 39% of Japanese men with a history of hypertension and myocardial infarction. In hypertensive patients undergoing cardiac catheterization, preexistent azotemia has been identified as a predictor of ARAS. 3° In another study of 201 patients receiving lower extremity arteriography, coronary artery disease was the only clinical predictor of renal artery stenosis, a3 The presence of RAS may also signify an increased risk of cardiovascular events. In 1 series of 86 patients ~ver the age of 70 presenting with New York Heart Association class II to IV heart failure, 34% were found to have stenosis of at least 50% involving at least 1 renal artery. 3~

Atheromatous RAS is also highly prevalent in patients with renal insufficiency, and when be- lieved to be the etiology for the renal disease is Lermed ischemic nephropathy. In a prospective evaluation of 21 azotemic patients (serum Cr -> 2.0 mg/dL) older than 45 years old, O'Neil et all found RAS in 14%. The presence of RAS was associated with a more rapid decline in renal function and ~ignificantly more extrarenal atherosclerosis. Renal artery stenosis is also an increasing cause of end-stage renal disease (ESRD) requiring renal replacement therapy. Appel et al 2 noted that 10 of 45 (22%) ESRD patients had renovascular disease ?n duplex sonography, and in an audit of patients presenting to a renal unit at the Royal Free Hospi- tal in the United Kingdom, atherosclerotic renovascular disease was the cause for renal failure in 14% of patients over the age of 50. 3 Furthermore, patients with ESRD resulting from RAS appear to nave the worst prognosis of any dialysis patient group. Mailloux et a132 noted that these patients .~ad only a 27-month median survival, with a 5-year survival of 18%, corresponding to an ap-

proximately 30% per year mortality. Renovascular ESRD also poses a tremendous economic burden. According to the 2001 USRDS, 33 there were 80,128 incident ESRD patients in 1999, with an average cost of $36,600 per annum. 34 If 14% of these patients have a renovascular cause of ESRD, then this amounts to a fiscal responsibility of $410.5 million dollars per year in the United States alone.

CLINICAL PRESENTATION

Several clinical clues may alert the clinician to the presence of RAS (Table 2). These include sudden onset of hypertension; onset of hypertension before the age of 30 or after 50; and malignant, accelerated, or drug-resistant hypertension. Hypertension without a family history in patients who smoke or have systemic atherosclerosis also increases the likelihood of RAS. 35 On physical examination, a characteristic holosystolic flank murmur is associated with RAS in 55% of patients, 36 and more than 30% of patients with advanced Kimmelstiel-Wilson retinopathy will have renovascular hypertension. 37 Mild proteinuria frequently occurs in association with RAS, but severe proteinuria is usually more indicative of underlying intrinsic renal disease, and the degree of albuminuria inversely correlates with renal functional outcomes after revascularization. 38 Hy- pokalemia may also be noted in patients with RAS secondary to aldosterone mediated urinary potas- sium excretion and was present in 15% of patients in the US Cooperative study. 39,4° Finally, a dis- crepancy in size between the 2 kidneys of more than 1.5 cm should prompt an investigation for the presence of RAS.

Renal insufficiency induced by an angiotensin- converting enzyme inhibitor or angiotensin II receptor blocker is a strong indicator of bilateral or solitary RAS, presumably because of reduced glomerular filtration after inhibition of angiotensin

Table 2. Clinical Features of RAS

History Physical examination Laboratory

Onset <30 or >50 yr old Malignant, accelerated, drug resistant hypertension Smoking Systemic atherosclerosis No family history of hypertension ACE1 or ARB induced renal failure Unexplained or rapidly progressive renal failure Recurrent pulmonary edema

Epigastric bruit Retinopathy Asymmetric renal size

Hypokalemia Mild or absent proteinuria Elevated plasma renin activity

Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker.

RENAL VASCULAR INTERVENTIONS

Table 3. Anatomical Indications for Renal Revascularization

315

Indicators for PTRA: -> 50% diameter RAS with a translesional pressure gradient of at least 20 mm Hg > 80% diameter RAS, without measuring translesional gradient patent intrarenal arteries without significant or multiple stenosis (ie, viable kidney) target kidney >7 cm in length

Stenosis greater than 70%-80% may be considered for prophylactic intervention (in the absence of clinical indicators) to empirically prevent the progression of the stenosis to occlusion (approximately 5%/yr risk), particularly if the entire renal functional mass is at risk

Indications for renal stenting: Failure to attain a hemodynamically satisfactory result by renal artery angioplasty

>30% diameter residual renal artery stenosis Greater than a 20 mm Hg residual peak systolic pressure gradient Presence of a f low limiting dissection of the renal artery

Restenosis (>50%) of a lesion that was successfully treated by angioplasty in the past, with recurrent clinical symptoms Primary treatment of ostial RAS because of overhanging aortic plaque

II-induced constriction of the efferent renal arte- riole. Similarly, renal failure precipitated by a reduction in blood pressure in response to other classes of antihypertensive medications suggests the presence of RAS, as does any unexplained or sudden deterioration of renal function. Recurrent flash pulmonary edema out of proportion to abnor- malities of left ventricular ejection function is a recognized phenomenon occurring in patients with ARAS and is most likely secondary to intravascu- lar volume expansion and ventricular diastolic dysfunction. In a series of 55 consecutive azotemic patients, Pickering 36 found recurrent pulmonary edema in 25%. Pulmonary edema usually resolves after successful revascularization. 41,42

BACKGROUND AND INDICATIONS FOR PERCUTANEOUS INTERVENTION

Percutaneous transluminal renal angioplasty (PTRA) was first described by Grundzig et a143 in

1974. Although the placement of metallic endoprostheses to restore arterial patency was envi- sioned by Dotter and Judkins 44 in 1964, it was more than 2 decades later that Palmaz et al45 first reported the use of metal stents for the treatment of RAS. Initial clinical series in Europe by Kuhn et a146 and Joffre et a l , 47 a s well as the early results of the US multicenter trial, 48 established renal artery stenting (PTRS) as an important treatment adjunct in patients failing balloon angioplasty alone. Since that time, PTRA and PTRS have become widely accepted as a first-line therapy for many patients suffering from symptomatic RAS.

Ideally, patients being considered for renal revascularization should have both anatomic (morphologic) and clinical criteria for intervention (Ta- bles 3 and 4). In approaching these patients, the decision to pursue revascularization is often difficult, and several questions need to be considered.

Is revascularization possible and safe? Bilateral

Table 4. Clinical Indications for Renal Revascularization

Hypertension (88-91) accelerated hypertension-sudden worsening of previously controlled hypertension refractory hypertension-hypertension resistant to treatment with at least 3 medications of different classes including a diuretic malignant hypertension-hypertension with coexistent evidence of end-organ damage, including left ventricular hypertrophy,

congestive heart failure, visual or neurological disturbance, and/or advanced (grade IV) retinopathy hypertension with a unilateral small kidney hypertension with intolerance to medication

Renal salvage sudden unexplained worsening of renal function 1921 impairment of renal function secondary to antihypertensive treatment, particularly with an angiotensin converting enzyme

inhibitor or angiotensin II receptor blocker (93,94) renal dysfunction not attributable to another cause

Cardiac disturbance syndromes recurrent flash pulmonary edema out of proportion to left ventricular impairment (95-97) unstable angina in the setting of significant RAS

Medication flexibility clinical need to use ACEI or ARB (ie, for treatment of proteinuria or cardiac dysfunction) that would be otherwise

contraindicated due to risk of inducing renal failure intolerance to antihypertensive medications


iliac/femoral occlusions or severe aortic atherosclerosis are relative contraindications to intervention, with the latter likely to be associated with a greater risk of cholesterol or atheroembolism. Al- though certain renal artery lesions are better treated from an axillary or brachial approach, this is accompanied by higher puncture site-related and upper extremity neurologic complications. In patients with equivocal stenoses or in patients at an unusually high risk of atheroembolism because of an aortic aneurysm or marked aortic irregularity, a determination of renal vein renins (RVR) may be considered, and a positive study is highly predic- tive of a beneficial response to revascularization. 49 In patients with azotemia, the size of the kidney to be revascularized should be evaluated. Kidneys less than 7 cm in length do not usually warrant revascularization, 5° particularly if nonfunctional on a radionuclide renal scan, having markedly increased echogenicity and cortical thinning on ultrasonography, or associated with progressive advanced azotemia (serum creatinine > 4.0 rag/ dL). The condition of the intrarenal vessels on arteriography may also preclude intervention. Hy- pertensive patients with an atrophic kidney should have RVRs determined and treated either with catheter-directed ablation 51 or surgical nephrec- tomy if the RVR lateralizes to the affected side.

What are the reasons for treatment? As noted in table 3, there are many different reasons for performing renal revascularization. The importance of treatment must be weighed against potential risks. Angioplasty or stenting of an incidentally discovered <80% diameter RAS without a good clinical indicator is rarely warranted. In contradistinction, because of the documented high risk of occlusion in untreated lesions exceeding 80%, 52,53 prophylactic revascularization can be justified in this setting, particularly if the entire renal mass is jeopardized by renal ischemia. This strategy may allow intervention at an earlier stage before the development of a more technically challenging higher-grade stenosis or occlusion and before ir- reversible critical loss of functional renal paren- chyma. 54

When treating azotemic patients, what it the risk of progressive renal insufficiency with and without intervention? Chabova et a155 in a recent study found that only 9% of patients with renal insufficiency followed for 3 years progressed to renal replacement theory, with a higher rate of progres-

sire azotemia in individuals with bilateral disease. This relatively low risk of clinical disease progression, particularly in mildly azotemic patients with only unilateral disease, needs to be considered before undertaking revascularization. Although several reports support the concept that better stabilization of renal function is seen after revascularization in patients with more mild levels of renal dysfunction, 56-5s it is not clear whether this is because of intervention or inherent to the natural history of the disease. Furthermore, no thresholds for this effect have been defined, and it remains to be determined whether there is an impact of revascularization on overall dialysis-free survival in azotemic patients. Finally, even with the use of renal protective agents 59,6° and alternative contrast agents, intervention has an approximately 2% to 5% risk of aggravating renal dysfunction.

TECHNIQUE OF RENAL ANGIOPLASTY AND STENTING

When performing renal interventions, careful preintervention planning is necessary to assure the highest possible technical success. The best route for crossing the lesion should be carefully as- sessed. Arteries with a sharp caudal angulation from the aorta are often best approached from the axillary or brachial artery (Fig 2). For mild or equivocal lesions, translesional pressure measure- ments should be performed to confirm the hemo- dynamic significance before intervention.

Pharmacologic adjuncts are important for preventing procedure-related complications. Patients should be adequately hydrated. If PTRA or stenting is anticipated, acetylsalicylic acid (81 mg) is given beginning the day of the procedure. Heparin sulfate should be administered to provide full anticoagulation before crossing the renal artery stenosis (as a 3,000-10,000 U initial bolus) as well as periodically during continued catheter and de- vice manipulation (as an additional bolus of 1000 U/h). If available, measuring the activated clotting time is useful to assure adequate levels of anticoagulation. The use of protamine sulfate to reverse heparinization after the procedure should be avoided because this may risk hypotension and acute stent thrombosis. Once the lesion is crossed, intra-arterial nitroglycerin should be liberally de- livered through the catheter in 100 to 200 /xg aliquots to prevent wire and catheter-induced va- sospasm. Intra-arterial verapamil (1-2.5 mg) is

RENAL VASCULAR INTERVENTIONS 317

very effective for treating spasm resistant to nitroglycerin but should be used with caution in patients with first-degree heart block.

Angioplasty is performed using well-established techniques, s Although only the basic concepts will be mentioned in this article, technical tricks for performing complex renal stent cases have been described61(Fig 3). Once a stenosis is identified by aortography, the lesion is carefully and atraumati- cally crossed by using a floppy-tipped guidewire and appropriately shaped shepherds crook or co- bra-shaped catheter. Depending on the balloon or stent system used, exchange is then made for a stiffer wire to facilitate subsequent catheter manip- ulations. The shortest possible balloon with a

Fig 2. Access site for renal intervention. (A) The right renal artery shows a sharp caudal angulation from the aorta. This was approached from a brachial access site. The left renal artery has a transverse orientation and is best approached from a femoral access. (B) The left renal artery stent has been deployed. A balloon expandable stent is positioned from a brachial approach over the right renal artery stenosis. {C) Postangioplasty and stenting views shows the marked caudal angulation of the right stent and the transverse postioning of the left renal artery stent.

diameter equal to the normal width of the target renal artery is positioned across the stenosis and slowly inflated, with care taken to avoid balloon sliding that may risk dissection. After deflation, the balloon is removed while maintaining guidewire position across the treated site. Completion angiography is performed by a guiding catheter or sheath, or more rarely, using a pigtail catheter introduced parallel to the guidewire or from a different vascular access site. If there is a satisfactory angiographic appearance and no residual transstenotic gradient, the guidewire is carefully removed.

Despite the use of stents in the renal arteries for more than 10 years, trials are still underway to obtain approval by the US Food and Drug Admin-


Fig 3. Kissing balloon renal angioplasty. The patient is a 60-year-old man with renovascular hypertension. (A) Initial selective right renal angiogram demonstrates a lesion at the bifurcation of the anterior and posterior renal artery, (B) Using 2 coronary 3-mm balloons, a "kissing" angioplasty was performed. (C) Post-PTRA image shows successful resolution of the stenosis with preservation of flow in both branch vessels.

istration for renal indication. Despite this, stenting is in many centers considered the standard of practice for the treatment of most atheromatous renal artery lesions. In fact, because in part of the universal recognition and success of coronary stenting, there is tremendous peer pressure by referring physicians in many practices to place a renal stent rather than perform PTRA alone. The 2 major stent types used for PTRS are balloon expandable and self expandable, with the greatest worldwide experience and the results reported in almost all US series being with the balloon-expandable Palmaz stent (Cordis Corp, Warren, NJ) and its subsequent modifications. Newer genera- tions of stents using lower profile delivery systems and stent designs intended to improve the ease and accuracy of placement are available in traditional over-the-wire platforms as well as rapid-exchange monorail systems.

Placing renal stents is associated with a set of considerations not normally encountered with PTRA alone. Although angioplasty does not usually affect subsequent surgical renal artery re-

vascularization, stenting can. Stents in the ostial location prevent the performance of transaortic endarterectomy, whereas the placement of stents further out in the renal artery will severely limit the options for subsequent surgical reconstruction. Po- sitioning the stent in the stenosis is of utmost importance and is much more critical than in angioplasty alone. Finally, because of the very rare but potentially devastating risk of stent infection, some operators recommend pretreatment with broad-spectrum antibiotics before PTRS. 6z63

The shortest possible stent that will cover the target lesion plus 1 to 2 mm on each side should be used. This prevents potential injury to a nondis- eased portion of the artery and preserves the option for a future surgical bypass should the stent fail. Balloon-expandable stents may be either pre- mounted or hand crimped onto a balloon catheter. The major technical problem is malpositioning of the stent. 64,65 It is essential that the renal artery is imaged in the proper oblique so the lesion is exactly in profile, especially if the lesion is ostial (Fig 4). The goal is to place the stent so that it


Fig 4. Profiling. It is important to image the renal arteries in the proper obliquity, especially for an ostial lesion. (A) The right renal artery is often best imaged from a straight anterior- posterior image. (B) The left renal usually arises obliquely from the aorta. This is best visualized with a 20 ° to 40 ° left anterior oblique image. (C) Computed tomograpy image after stenting shows the angle of origins of the renal arteries from the aorta. (D) Oblique view on angiography show the marked shortening of the right renal stent when viewed in the left anterior oblique (LAO). The right renal ostium is best visualized in anterior- posterior or right anterior oblique (RAO).

covers the lesion and extends 1 to 2 mm past it on both sides; for ostial lesions, the proximal end should extend 1 to 2 mm into the aorta to ensure that it covers the ostium adequately. As with angioplasty alone, the completion angiogram after stenting should be performed with a technique that preserves wire position across the stenosis to facilitate repeated interventions including further stent dilatation or placement of additional stents. This also decreases complications by obviating the need to recross the lesion in the event of a dissection or other vessel injury.

COMPLICATIONS AND THEIR PREVENTION

Complications of PTRA and stenting are reported to occur in 5% to 10% of patients and include spasm, thrombosis, dissection, and embolization. 66,67 The routine use of adjunctive anti- spasmodic medications and heparin helps prevent the first 2 of these problems. Acute occlusion is rare and is usually caused by dissection or thrombosis. Angiographic distinction of these 2 entities will allow appropriate treatment with stents or thrombolysis, respectively. Frank rupture with ret-

roperitoneal extravasation of contrast requires surgical repair, although there is recent experience with the successful use of stent grafts. The PTA balloon or an occlusion balloon should be inflated across the site of rupture until definitive therapy is undertaken. Iced saline can be infused through the catheter to help preserve the kidney while the operating room is readied. If this does not control the hemorrhage a large occlusion balloon can be inflated across the renal origin. In contrast, perfo- ration by only a guide wire is almost always self-sealing, and peripheral perforations that do not stop bleeding can be treated with subsegmental transcatheter occlusion using coils or gel foam.

One of the major potential complications with renal angioplasty is the embolization of cholesterol crystals or atheromatous plaque. Microcholesterol crystal embolization occurs in approximately 1% to 2% of patients and is potentially severe or even fatal. Patients with marked aortic irregularity are at particular risk. Unfortunately, there is no specific treatment for cholesterol crystal embolization. Careful patient and access-site selection and greater operator experience can help minimize the


risk, as can the use of soft-tipped catheters and guide wires. Symptomatic distal embolization of dislodged large plaque is rare but may require surgical embolectomy, bypass, or thrombolysis.

Transient contrast-related declines in renal function may be seen in up to 13% of patients undergoing renal interventions. 68 The risk factors for renal failure after administration of iodinated contrast material are well known and include preex- isting renal insufficiency, dehydration, diabetic nephropathy, hyperuricemia, and multiple my- eloma. Fortunately, in patients with normal renal function, the risk of permanent renal impairment is small. Alternative contrast agents including gado- linium and CO 2 are routinely used in patients with marginal renal reserve. In addition, premedication with mucomyst or fenoldopam may decrease the renal toxicity of iodinated contrast material. 59,6°

POSTPROCEDURE CARE

Every patient should be closely monitored after renal intervention. Immediately after procedure patients are well hydrated. Blood pressure, volume status, urine output, and serum creatinine are monitored closely. Acute deteriorations of renal function may warrant repeat angiography, further intervention, or bypass. Patients are generally advised to take an antiplatelet agent (eg, acetylsalicylic acid 81 mg daily) postprocedurally. Although the use of other antiplatelet medication such as ticlo- pidine, clopidigrel, dipyridamole, and cilostazol have shown clinical promise for preventing progressive vascular stenosis in other vascular beds, 69-7j their role after renal interventions is not yet established. Routine systemic anticoagulation is not used except in patients with known hyper- coagulable states. If the patient has persistent or increasing back or flank pain, arterial rupture or impending rupture as well as total occlusion must be considered, and a computed tomography scan is warranted to look for extravasation around the renal artery and kidney.

TECHNICAL RESULTS OF RENAL ANGIOPLASTY AND STENTING

PTRA has become well established for the treatment of RAS caused by fibromuscular dysplasia, with reported rates of technical success ranging from 88% to 100% and hypertensive benefit in 79% to 100%. 72-74 Similarly, excellent immediate- and long-term results can be achieved for PTRA of

nonostial atheromatous RAS, with an overall clinical benefit that is often related to such factors as renal size, comorbid medical conditions, and coexistent essential hypertension. 75-84 Despite this, the role of PTRA in treating patients with atherosclerotic RAS has remained controversial, primar- ily because of the poor technical success and high restenosis rates of PTRA alone for the treatment of ostial lesions in most series. 85-89 Stenting has improved the technical success of PTRA for these eases 9°,91 by providing a scaffold that displaces aortic atheroma. In a prospective randomized trial, Van de Ven and associates 91 reported a primary success rate of 88% for PTRS compared with 57% for PTRA. In ostial lesions, the radial force of the stent counteracts the elastic recoil and geometric remodeling that are significant contributors to both early and late restenoses. 92,93 Furthermore, stents produce a smoother luminal surface that is theo- retically less likely to cause platelet aggregation, smooth muscle cell stimulation, and intimal hyperplasia (IH). 94,95 For this reason, several investigators have advocated the increasingly common practice of primary stenting of ostial lesions. 68,96,97 In contrast, other investigators, using strictly defined criteria for ostial lesions, have noted that a smaller than previously thought proportion of these ostial stenoses are actually because of aortic plaque. 98 Furthermore, although supported by retrospective series, it has not been definitively shown that stenting results in improved long-term patency when compared with a perfect response after PTRA alone. 99-1°2 Prospective long-term studies are needed to firmly answer this question.

After stenting, restenosis caused by IH occurs in approximately 16% of treated arteries. ~o3 Since the development of approximately 1 mm of IH cover- ing the stent surface is a normal part of stent healing (Fig 5), the risk of restenosis is geometri- cally related to the initial degree of stent expansion. In the US multicenter study, stents dilated to less than 6 mm had nearly double the risk of restenosis. 1°4 A significantly higher rate of restenosis was also observed in smokers and in women, whereas the effect of gender was not confirmed in 1 other study. ~°5 Van de Ven et al 9~ reported restenosis in 48% of patients treated by PTRA versus 14% after stent placement, although there were no differences in clinical outcomes between the 2 groups. Of note, even modest levels of restenosis may be an important cause of clinical


Fig 5. Intimal hyperplasia after renal artery stenting. The right renal artery stent was placed 1 year previously. Note is made of intimal hyperplasia separating the lumen of the vessel from the stent, The left renal artery was stented at this time, and there is close apposition between the stent and the vessel lumen,

failure after PTRA alone in azotemic patients with small vessel diameters and/or atherosclerotic renovascular disease involving the entire functional renal massJ °6 Thus, liberal stenting in these patients should be considered.

CLINICAL RESULTS OF RENAL ANGIOPLASTY AND STENTING

The weighted clinical results from larger series of PTRA and PTRS procedures are shown in Tables 5 and 6. 57,58,68,78,83-85,88,96,97,101,103,107-121 Af-

ter stenting, hypertension benefit is noted in 72% of patients 1 year after successful treatment. Renal

intervention is often drug sparing and has the important advantage of improving blood pressure medication flexibility, particularly by allowing the use of angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, t22,123 The clinical results of PTRS for hypertension are slightly infe- rior to those published for surgical revascularization, although there is a considerably higher morbidity and mortality in patients treated by surgery. In a recent cumulative review of surgical series, hypertensive benefit was seen in 86% of patient with long-term observation, 124 although the surgical mortality was 4.3%. In addition, a prospective randomized study of PTRA and surgery noted almost twice the rate of major complications in the surgical group (31% v 17%). 125

Several publications have questioned the value of renal artery angioplasty compared with medical therapy alone. 126-~28 Unfortunately, each of these small series was methodologically flawed, had limited statistical power, and did not include the use of stenting for angioplasty failures, and thus do not accurately reflect contemporary practice. In the largest of these series by van Jaarsveld et al, 126 44% of patients randomized to medical therapy crossed over during the study and were treated with PTRA; however, because of an intention-to- treat analysis, hypertensive benefits were attributed to medical therapy alone. Despite this, these investigators found that patients undergoing percutaneous revascularization were more likely to have 12-month blood pressure improvement (68% v 38%) or cures (7% v 0%) and less likely to have

Table 5. Results of PTRA for ARAS

First Author

Hypertension (%)

Cured Improved

Renal Function (%)

Improved Stabilized

Rodriguez-Perez I°7 37 3.5 75 Julien 1°8 53 9 70 Klinge 78 134 10 68 Canzanello a8 100 4 39 Martinez-Amenos 1°9 74 13 48 Jensen 85 107 12 40 Martin TM 110 10 48 Tegtmeyer 84 65 23 71 Lossinno 11° 153 12 51 Karagiannis TM 62 19 52 Belp16 Pattison 117 Pattynama ~8 Madias 1~9 O'Donovan 120 Luft85 Totals 895 11 54

79 43(61 b/I) 40 45 60 27(48 b/I) 67 27 15 33 20 35 50 60 40 50 40 60 12 38 16 17 41 24 12 50

367 39 46


Table 6, Contemporary Results of Larger Series of Renal Stenting

Hypertension (%) Renal Function (%}

First Author n Cured Improved n Improved Stabilized

lannone 97

White aa

Bium 103

Tuttle 112

Oorros 6s

Henry 113 184 19 Rocha-Singh TM 127 6 Rodriguez-Lopez 115 108 11 Siablis l~e 62 62 Totals 937 9

54 4 35 22 36 46 I00 76 44 22 78 68 16 62 20 100

129 2 53 97 13 105 1 42 106 33(U/L)

38(b/L) 61 48 29 50 71 28 57 32 100

8 0 100 63 448 26 60

76

33 (U/L) 42 (b/L) 67 59

blood pressure deterioration (9% v 33%) or progression to renal artery occlusion (0% v 16%).

Renal intervention has clinical benefit in the majority of patients treated for ischemic nephropathy, particularly for slowing the decline in renal function. 129-131 Patients in whom there is rapid decline in function before intervention have the greatest chance of renal improvement.132-J 34 Over- all benefit is noted in close to 90% of patients and is directly related to the pretreatment glomerular filtration rate. In a large multicenter registry com- prising 1,058 successful stent insertions, patients having higher initial creatinine levels (>2.0 rag/ dL) were more likely to stabilize than to improve renal function# 8 Using life-table analysis, Rund- back et aW report noted stabilization or improvement in renal function at l-year follow-up in 84% of patients whose initial serum creatinine was 1.5 to 2.0 mg/dL compared with only 38% when the serum creatinine exceeded 3.0 mg/dL. 57 Unilateral PTRS appears to provide equivalent clinical benefit to bilateral revascularization, although most investigators recommend bilateral intervention if it is technically feasible and both kidneys are of reasonable size. 57,136 The coexistence of diabetes mellitus does not adversely affect clinical outcomes. 137

The usefulness of renal revascularization in patients with recurrent episodes of flash pulmonary edema has been described. 41,4ml39 Bloch et a141 treated 25 patients with a history of congestive heart failure. At a mean follow-up of 18 months, 77% of patients receiving bilateral stents and 33% treated by unilateral PTRS had no recurrence of pulmonary edema. 4~ Khosla et al~39 have also noted renal artery stenting to be beneficial in patients with unstable angina. 137 In their small experience, 9 of 12 (75%) patients undergoing both

PTRS and coronary angioplasty had sustained improvement in angina compared with 4 of 6 (67%) patients treated by PTRS alone.

COST-EFFECTIVENESS OF PTRS

PTRA and PTRS are cost-effective in comparison to surgery. Weibull et a1125 prospectively studied 58 nondiabetic patients randomized to either PTRA (n = 29) or surgical revascularization (SR, n = 29). No stents were used in this series. Even though 31% of the PTRA ultimately required SR (17% because of technical failure of PTRA alone), PTRA was still 12% less expensive. More recently, Xue et al ~4° reported a retrospective cost analysis of PTRA, stenting, and bypass surgery at a single tertiary care center. At 1-year follow-up, equivalent clinical outcomes were seen in all 3 patient groups, although the complication rates were significantly higher in the patients treated by surgery. Predominantly because of higher proce- dural costs and longer hospital stays, SR costs almost 7 times more than PTRS and nearly 15 times the cost of PTRA. These data further support the role of PTRA and PTRS as the initial treatment in patients with symptomatic RAS.

CONCLUSION

Percutaneous renal revascularization has been practiced for 25 years. PTRA and PTRS allow successful and durable renal revascularization in nearly all cases and provide a favorable clinical outcome for the majority of treated patients. How- ever, several important areas of further investigation are necessary. There is still controversy con- cerning the effect of renal revascularization on cardiovascular events, dialysis-free survival, and overall mortality. 13,68,141 Studies are under way to answer these questions (Cooper C, personal corn-


munication). t42 N e w genera t ions of vascular s tents

and embol iza t ion pro tec t ion devices need to be

tes ted for their re la t ive ease o f use and cl inical

efficacy. The role o f drug-e lu t ing stents, wh ich

have s h o w n great p romise in other arterial beds , 143

needs to be evaluated. E m e r g i n g b iochemica l

markers o f R A S represen t in t r iguing resea rch tools

to bet ter unders tand renovascu la r pa thophys io l -

ogy 144J45 and prov ide the theoret ic potent ia l o f

predic t ing the r e sponse to revascular izat ion. Fi-

nally, r a n d o m i z e d prospec t ive trials are necessary

to def ine the proper pat ient select ion, l ong- t e rm

outcomes , and bes t me t h o d s of t rea tment for pa-

t ients wi th renovascu la r disease.

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Renal vascular interventions