Renal Artery Angioplasty

Percutaneous transluminal angioplasty (PTA) of the renal artery has become an increasingly widespread peripheral vascular intervention for the treatment of renovascular hypertension (HTN). Catheter-based procedures began in 1964 when Charles Dotter initially developed PTA for treating peripheral vascular atherosclerosis. Andreas Grüntzig revolutionized the technique in 1974 when he developed a soft, flexible, double-lumen balloon catheter for use in coronary arteries.

PTA has since rapidly evolved into a widely used, versatile, and dependable vascular interventional technique. Excellent results may be achieved in the renal arteries if patients are well selected and if experienced clinicians perform the procedure. (See the images below.)

Percutaneous transluminal angioplasty.

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Renal arteriogram obtained after renal percutaneous transluminal angioplasty.

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Renovascular HTN and renal PTA

In the United States, renovascular HTN is present in approximately 4% of the total population of persons with HTN. It is associated with increased morbidity because patients with severe HTN who have renovascular HTN are at increased risk for renal insufficiency.

Traditional therapeutic modalities that include drug therapy and surgical revascularization have too many shortcomings. Medicines frequently fail to adequately control the patient's blood pressure (BP) adequately despite polypharmacy, and they may cause undesirable adverse effects. Patients may be noncompliant with pharmacotherapy. Moreover, lowering BP in the presence of severe renal stenosis may lead to ischemic renal atrophy.

Surgery imparts considerable morbidity, and results vary. The associated need for general anesthesia may cause complications in patients, who are often poor candidates because of diffuse atherosclerosis or renal insufficiency. Nonetheless, the correction of renal stenosis is considered the treatment of choice whenever feasible.

Since its introduction in 1978, percutaneous transluminal renal angioplasty (PTRA) has emerged as a highly effective technique for the correction of renal artery stenosis (RAS). Renal angioplasty has notable physiologic, psychological, and economic advantages over other treatment modalities, and it should be considered the therapy of choice for renovascular HTN. ^{[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11]}

Alone or in combination with stent implantation, PTRA is increasingly used as an alternative to surgical revascularization for the treatment of RAS, which may cause HTN or jeopardize renal function. Technical success is usually achieved in more than 85% of cases; the failure rate is 10%.

PTRA-related complications occur in 7% of patients (see Technique). An overall benefit on BP control is observed in 20-40% of patients with atherosclerotic RAS (ARAS) and 60-70% of those with fibromuscular dysplasia (FMD; see Outcomes). Independent of etiology, PTRA appears to be technically effective in correcting RAS. However, its position with respect to medical or surgical treatment must be better defined through randomized controlled studies aimed at comparing the clinical efficacies of these approaches. ^{[12, 13, 14]}

Etiology of renal artery stenosis

RAS has multiple causes, but most lesions are the result of atherosclerosis. FMD is the second most common etiology. ^[15] (See the image below.)

Renal artery stenosis in patient with medically refractory renovascular hypertension.

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The incidence of RAS in patients undergoing cardiac catheterization is as follows:

• RAS occurs in 62% of patients with peripheral vascular disease (PVD) and HTN ^[16]
• RAS is found in 33% of patients with coronary artery disease (CAD)
• About 18% of patients with CAD have stenoses of greater than 50% ^[17]
• Both CAD and renal insufficiency are independent predictors for RAS
• The incidence of bilateral RAS is approximately 46% ^[18]

Regarding asymptomatic RAS, as many as 50% of patients with RAS do not have HTN. The incidence of progression of RAS is variable, but progression occurs in most patients. The overall progression rate is 49%, with 14% of patients developing total occlusion. Serum creatinine values do not adequately mirror progressive anatomic disease, and control of HTN does not thwart progression of RAS. The absence of HTN after PTRA does not preclude restenosis.

RAS is frequently underdiagnosed.

ARAS is a common condition that is often but not necessarily associated with HTN. Because of its progressive nature, ARAS is becoming one of the leading causes of end-stage renal disease (ESRD). Indeed, ARAS is reported to progress within 5 years in 51% of patients, and renal atrophy develops in 21% of patients in whom ARAS is initially greater than 60% of the caliber of the vessel.

RAS may occur in the setting of a transplant (transplant RAS, or TRAS) and is often treated with endovascular techniques. ^{[19, 20, 21]} A study by Chen et al found stenting to be superior to angioplasty alone for treating TRAS. ^[22]

Indications for PTRA

The indications for renal angioplasty are evolving. The common indications are as follows ^[23] :

• Sudden onset of HTN
• HTN in a patient without a positive family history
• HTN in a patient without a medical history of factors known to cause HTN
• Malignant HTN
• HTN refractory to pharmacotherapy
• Patient noncompliance with medications
• HTN in a patient with abdominal bruit suggestive of renal artery narrowing
• HTN in a patient who develops renal failure while taking captopril
• Sudden-onset HTN in a young woman not taking oral contraceptives (for patients in this group, the likelihood of FMD is increased)

Indications for PTRA or renal stenting

Indications for PTRA or renal stenting include the following:

• Progressive decline in renal function
• Accelerated or difficult-to-control HTN - Presence of greater than 75% RAS and one of the following: (1) HTN requiring three or more medications for control, (2) HTN on treatment with mean BP greater than 110 mm Hg, (3) chronic renal insufficiency with creatinine below 3 mg/dL, or (4) acute renal failure with preserved renal size and echogenicity on ultrasonography (US)

Other expanding indications include the following:

• Congestive heart failure (CHF)
• Unstable angina
• Recent development of ESRD that is partly the result of RAS (the patient may be able to avoid dialysis)
• Angiographic lesion in the absence of HTN or renal insufficiency ^[24]
• Patients with unstable angina or CHF and refractory HTN and up to 70% stenosis of one or both renal arteries (in one study, renal stenting resulted in dramatic improvement independent of coronary angioplasty ^[25] )
• High-grade RAS in patients undergoing infrarenal abdominal aortic aneurysm repair ^[26]

Renovascular disease: clinical indicators

Clinical indicators of renovascular disease are as follows:

• HTN - Onset before age 30 years or after age 50 years; abrupt onset; history of CAD; history of tobacco abuse; absence of family history of HTN; presence of abdominal bruit 4-5 cm lateral to midline
• Pulmonary edema or renal insufficiency - Bilateral renal artery disease; RAS in a single kidney; treatment with an angiotensin-converting enzyme (ACE) inhibitor (may cause sudden azotemia)

These epidemiologic data emphasize the need for an aggressive diagnostic approach and treatment of ARAS, for the treatment of HTN, and for the prevention of ischemic nephropathy. These goals may be achieved, to some extent, with PTRA.

Contraindications for PTRA or renal stenting include the following:

• Advanced disease - Creatinine level greater than 3-4 mg/dL (recommendations vary); kidney length less than 8 cm
• Limited life expectancy
• Generally poor surgical or PTRA candidate - Bleeding diathesis; recent myocardial infarction (MI)
• Pregnancy

Clinical success rates

Several published series have reported clinical results obtained with angioplasty. ^{[27, 28]} (See Table 1 below.)

Table 1. Success Rates of Percutaneous Transluminal Renal Angioplasty (PTRA) in Renal Artery Stenosis (RAS) Caused by Atherosclerosis (80% of RAS) and Fibromuscular Dysplasia (FMD; 20% of RAS) ^{[27, 28]} (Open Table in a new window)

*Ostial location is an independent predictor of poor outcome. Clinical success rates are 54% at 3 years, with high restenosis rates.

Fibromuscular dysplasia

When the cause of renal stenosis is FMD, the results of PTRA are uniformly good, with cure in about 58% of patients, improvement in 35%, and failure in 7%. These results are comparable to those obtained with surgery. Restenosis is uncommon in patients with this condition, and follow-up angiograms (< 5 years after angioplasty) often show no trace of stenosis.

Chen et al assessed the safety and efficacy of PTA with selective stenting in 105 patients (mean age, 26.7 ± 8.2 years; 49.5% female) who had RAS due to FMD. ^[29]  The technical success rate for endovascular therapy was 95.2% without severe complications. During 1-year follow-up, mean systolic and diastolic BP decreased from 157.6 ± 17.5 and 102.3 ± 14.2 mm Hg, respectively, to 129.6 ± 12.3 and 81.3 ± 11.1 mm Hg, respectively. The number of antihypertensive medications decreased from 2.2 ± 1.2 to 0.8 ± 1.0. The cure rate was 49.0%, and improved BP rate was 40.0%. Serum creatinine levels remained stable. The primary and secondary restenosis rates were 13.4% and 5.8%, respectively. 

Atherosclerosis

When atheroma causes the stenosis, the results of revascularization are not as good, with cure in 22% of patients, improvement in 57%, and failure in 21%, whichever modality (angioplasty or surgery) is used. Furthermore, in patients with diffuse atheromatous disease, the complication rate is relatively high with both surgery and angioplasty; for these patients, medical therapy may be preferred. The common indications for renal stenting include the following:

• Ostial stenosis
• Flow-limiting dissection of the renal artery after PTA
• Persistent significant gradient after PTA
• Restenosis after balloon angioplasty

Short balloon-expandable stents are usually used for renal stenting.

Clinical outcomes

Early decrease in blood pressure

In patients in whom PTRA is technically successful, a prompt decrease in BP is usually observed. ^[30] The mechanism of this early decrease is not understood. Plasma renin activity, norepinephrine, and muscle sympathetic nerve activity all increase in the first or second hour, despite the falling BP. This finding raises the possibility that some vasodilator substance is released.

In the atheromatous patients with unilateral stenoses, the eventual benefit rate (defined as improvement or cure of HTN 3 months after angioplasty) was 87%; in the FMD patients, it was 92%.

Patients with stenosis and a solitary kidney are excellent candidates; one series showed a benefit rate of 92% for such patients.

Effect on blood pressure in ARAS

Differences in the criteria used to select patients, in defining an improvement in BP, in the duration and modalities used for follow-up, and in medical treatment hamper any comparison of studies addressing the effects of PTRA on BP. Despite these limitations, authorities have generally agreed that for patients with ARAS, PTRA rarely leads to a reduction in BP.

In a review of the experience in 10 centers, 691 patients were treated with PTRA. About 19% were cured; BP improved in 51%; and BP was unchanged in 30%. In other reviews, the effects on BP were even less encouraging. For instance, 8% of several hundreds of patients with HTN were cured with PTRA. In a study by the present authors, 66 patients were followed up for at least 6 months; the patency of the dilated artery was confirmed mostly by means of echographic Doppler velocimetry. In these patients, the rate of cure was 3%, with a 38% rate of improvement.

The introduction of stents has not improved the outcome of PTRA with regard to BP. A 4-year follow-up study of 163 patients who were successfully treated with stent implantation showed that only one was cured; improvement was seen in 42%. These negative results are not surprising in consideration of the fact that the great majority of patients with ARAS have been exposed to the deleterious effects of high BP for years. Their HTN results in extensive renal and vascular damage, which prevents BP from returning to normal levels, even after the stenotic artery is dilated.

This conclusion obviously underscores the need for the careful selection of the few patients who may benefit from dilation procedures. For patients who do not fulfill the diagnostic criteria for real renovascular HTN and those in whom even PTRA is considered too risky, medical treatment permits the same degree of BP control that would be achievable with dilation. Indeed, three major studies comparing the effects of PTRA and medical treatment in patients with ARAS showed that the BP reductions obtained with the two approaches were similar (see Table 2 below). ^{[23, 31, 32]} The only advantage for patients treated with PTRA was diminution of their drug regimen.

Table 2. Success Rates of Percutaneous Transluminal Renal Angioplasty (PTRA) in Renal Artery Stenosis (RAS) Caused by Atherosclerosis (80% of RAS) ^{[23, 31, 32]} (Open Table in a new window)

In a retrospective study analyzing 224 patients treated with PTRA for primary symptomatic RAS at four tertiary centers, Zachrisson et al found that treatment led to significant reductions in mean systolic pressure (from 168 to 146 mmHg), diastolic pressure (from 84 to 76 mmHg), number of antihypertensive drugs (from 3.54 to 3.05), and antihypertensive treatment index (from 21.75 to 16.92). ^[33]  These improvements were maintained at 1 year and at the last clinical evaluation after a mean follow-up of 4.31 years. Renal function increased transiently without sustained improvement, or deterioration, during later follow-up.

Effect on renal function

Theoretically, PTRA should be used more for preserving renal function than for reducing BP. Given the progressive nature of ARAS, PTRA should be performed before ischemic damage to a kidney has occurred. Renal outcome with PTRA is better when renal function is still normal than when it is altered. In general, the overall cardiovascular risk for patients undergoing PTRA with a baseline serum creatinine level greater than 1.5 mg/dL is 5 times higher than that of patients with a creatinine level below that value.

So far, no medications have been shown to retard the progression of ARAS. On the other hand, the evidence has not supported the theory that PTRA improves renal function in patients with ARAS. ^[34] (See Table 3 below.)

Table 3. Natural History: Progression of Medically Treated Renal Artery Stenosis ^[34] (Open Table in a new window)

In a large meta-analysis, 25-53% of patients who underwent PTRA had some improvement in renal function. In another review of 215 patients with ARAS and mild renal insufficiency treated with stent implantation, 35% had improvement in renal function, as estimated by assessment of changes in serum creatinine level or creatinine clearance. In 35% of these patients, the condition was stabilized with the procedure.

Bax et al found that in patients with atherosclerotic renal artery stenosis, renal artery stenting had no clear effect on renal function impairment and led to significant complications in some patients. ^[35] The multicenter trial included 140 patients with creatinine clearance less than 80 mL/min/1.73 m² and renal artery stenosis of 50% or greater. All patients received medical treatment with antihypertensive agents, a statin, and aspirin.

Although 64 patients were randomized to stent placement, only 46 had the procedure; in many patients, assessment of RAS by noninvasive imaging was inaccurate, and stenting was in fact not indicated. ^[35] Progression of renal dysfunction, as indicated by a decrease in creatinine clearance of 20% or greater, occurred in 16% of patients in the stent placement group and in 22% of patients in the medication group. Serious complications in the stent group included two procedure-related deaths.

In a retrospective single-center study of long-term renal function, morbidity, and mortality, Zachrisson et al assessed 57 patients with symptomatic RAS who were treated with PTRA and followed for a median of 11 years and 7 months. ^[36]  The main indications for PTRA were therapy-resistant HTN and declining renal function. Patients were angiographically evaluated for restenosis at 1 year.

Over the course of follow-up, 36 patients (60%) died, mostly as a consequence of cardiovascular events (54%). ^[36]  At 1 year, 21 patients (37%) had angiographically documented restenosis. Control of HTN was stable over the follow-up period, with an ongoing need for antihypertensive medication. Renal function continued to be moderately reduced and did not differ between patients who had restenosis and those who did not.

Reinhard et al prospectively studied the effects of renal artery stenting on ARAS in 102 patients with high-risk clinical presentations. ^[37] ​ In the 96 patients for whom 3-month follow-up data were available, the mean 24-hour ambulatory systolic BP decreased by 19.6 mm Hg, the defined daily antihypertensive medication dose was reduced by 52%, and the estimated GFR increased by 7.8 mL/min/1.73 m². These changes persisted after 24 month follow-up.

Apparently, even for preserving renal function, PTRA should be performed only in patients who have been rigorously selected. ^[28] Patients who might benefit from PTRA should be evaluated to the same extent as those chosen for a possible antihypertensive effect. (See Table 4 below.)

Table 4. Effect of Renal Stenting on Serum Creatinine Level ^[28] (Open Table in a new window)

Markers of outcome

Unfortunately, there is no consensus regarding valid markers of a favorable renal outcome with PTRA.

One may use the radioisotopic technique, which allows an accurate evaluation of the split function of the two kidneys. This method may avoid the limitations inherent to assessments based on creatinine and creatinine clearance.

The preservation of renal function depends not only on the restoration of renal blood flow but also on the wearing off of other ischemia-induced mechanisms of renal damage that may fully regress only after a long period.

PTRA may affect the glomerular filtration rate (GFR) of the dilated kidney, as well as baseline values of peripheral plasma renin activity and angiotensin II (Ang II). These changes may suggest that the degree of activation of the renin system could be a predictor of the functional recovery of the kidney.

From a mechanistic point of view, this finding fits well with the notion that Ang II is essential for the maintenance of GFR. Indeed, if renin is released in proportion to the reduction in renal blood flow, it is entirely plausible that the ischemic kidneys exposed to the highest concentration of Ang II are also those in which the GFR may increase when the renal blood flow is restored with successful PTRA. ^{[32, 38, 39, 40, 41]}