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 Gruntzig 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 now be achieved in the renal arteries if patients are well selected and if experienced clinicians perform the procedure.

The images below depict PTRA.

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 an increased morbidity rate 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 BP adequately despite polypharmacy; medicines may cause undesirable adverse effects; and patients may be noncompliant. Moreover, lowering the BP in 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 stenoses. Renal angioplasty has notable physiologic, psychological, and economic advantages over other treatment modalities, and it should now be considered the therapy of choice for renovascular HTN.^{[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12]}

Alone or in combination with stent implantation, PTRA is increasingly used as an alternative to surgical revascularization for the treatment of renal artery stenosis (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 are observed in 7% of patients (see Complications section below). An overall benefit on BP control is observed in 20-40% of patients with atherosclerotic RAS (ARAS) and in 60-70% of patients with fibromuscular dysplasia (FMD; see Clinical Success Rates and Outcomes section below). Independent of the etiology, PTRA appears to be technically effective in correcting RAS. However, the position of PTRA with respect to medical or surgical treatment needs to be better delineated through randomized, controlled studies aimed at comparing the clinical efficacies of these different approaches.

Renal artery stenosis

RAS has multiple causes, but most lesions are the result of atherosclerosis. FMD is the second most common etiology.^[13] See image below.

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

1. RAS occurs in 62% of patients with peripheral vascular disease (PVD) and HTN.^[14]
2. RAS is found in 33% of patients with coronary artery disease (CAD).
3. About 18% of patients with CAD have stenoses of greater than 50%.^[15]
4. Both CAD and renal insufficiency are independent predictors for RAS.
5. The incidence of bilateral RAS is approximately 46%.^[16]

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.

Atherosclerotic RAS

Atherosclerotic RAS (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.

Indications for PTRA

The indications of renal angioplasty are still evolving. The common indications are as follows:^[17]

• 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 fibromuscular dysplasia [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 1 of the following:
    • HTN requiring 3 or more medications for control
    • HTN on treatment with mean BP greater than 110 mm Hg
    • Chronic renal insufficiency with creatinine less than 3 mg/dL
    • Acute renal failure with preserved renal size and echogenicity on ultrasonography
• Other expanding indications include the following:

  • Congestive heart failure (CHF)
  • Unstable angina
  • Recent development of ESRD partly the result of RAS (Patient may be able to avoid dialysis.)
  • Angiographic lesion in the absence of HTN or renal insufficiency^[18]
  • Patients with unstable angina or CHF and refractory HTN and up to 70% stenosis of 1 or both renal arteries (In 1 study, renal stenting resulted in dramatic improvement independent of coronary angioplasty.^[19] )
  • High-grade RAS in patients undergoing infrarenal abdominal aortic aneurysm repair^[20]

Renovascular disease: clinical indicators

Clinical indicators of renovascular disease are as follows:

• Hypertension (HTN)

  • Onset of HTN before age 30 years or after age 50 years
    • Abrupt onset of HTN
    • 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 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

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

Patient selection for PTRA

Renovascular disease is present in 10-40% of patients with ESRD, who constitute the fastest-growing group of patients with ESRD. Nonselective correction of RAS has led to disappointing results. Most groups that compared conservative treatment with angioplasty found only modest or no beneficial effects of angioplasty on renal function and BP.

Patients with a high likelihood of a favorable response should be identified. Factors that affect outcome include the severity of RAS; the procedure used to treat RAS (eg, antihypertensive drugs, angioplasty with or without stents, surgery); nephrotoxicity to radiologic contrast materials; atheroembolism^[21] ; and most importantly, underlying renal disease forestalling a favorable response in renal function or BP, even after the successful correction of RAS.

Renal resistance may be evaluated by use of Doppler ultrasonography or captopril scintigraphy to determine whether patients may or may not respond to intervention. Each factor must be considered before the correction of RAS to achieve satisfactory results in improving renal function and BP.

Diagnostic studies for renovascular disease

Diagnostic studies for renovascular disease include the following:

• Rapid sequence intravenous pyelography (IVP)

  • Sensitivity of 74.5%; specificity of 86.2%
  • Limited sensitivity for bilateral or branch RAS
  • False-positive rate of 12% in patients with essential HTN^[22]
• Test of the renin ratio in the renal vein

  • Sensitivity of 80%; specificity of 62%
  • Use of sodium depletion, hydralazine, nifedipine, and captopril may enhance asymmetric response and increase sensitivity without affecting specificity
  • Renal cysts, pyelonephritis, and ureteral obstruction may increase the asymmetry of renin secretion^[23]
• Radionuclide imaging

  • Sensitivity and specificity approximately 95% with use of captopril
  • Addition of furosemide may increase sensitivity
  • Severe renal insufficiency and the presence of bilateral RAS reduce the accuracy of the test^[24]
• Renal artery duplex ultrasonography (RADUS)

  • Sensitivity of approximately 98%, as compared with arteriography
  • Specificity of 98%
  • Technician dependent (drawback)
    • Up to 10% of patients cannot be imaged because of body habitus
    • Not universally available
  • Positive predictive value of 99%
  • Negative predictive value of 97%^[25]
• MRA (magnetic resonance angiography)

  • Likely to be the test of choice
  • Sensitivity nearly 100% and specificity nearly 90%^[26]
  • Limitations of nonportability; cannot be used in patients with implanted devices, metal artifacts, or claustrophobia, or in patients of certain size and weight
• Spiral CT (multisection CT) — Sensitivity and specificity not yet determined

Technique

• The technique for this procedure is described in the image captions below.Percutaneous transluminal renal angioplasty procedure in a middle-aged woman with malignant renovascular hypertension. This preprocedural right renal arteriogram was obtained after sterile preparation and draping of the patient, conscious sedation, infiltration of local anesthetic (lidocaine 1% or 2% solution) at the femoral access site, placement of an arterial sheath in the femoral artery, and advancement of the renal guide catheter over a 0.035-in guidewire under fluoroscopic guidance. After the tip of the guide catheter is positioned at the ostium of the renal artery, an angiogram (as shown here) is obtained. After the guidewire is removed, the proximal end of the catheter is connected to a manifold, and 4-8 mL of contrast is manually injected during cineangiographic recording. Once obtained, the image may be played over and over in a loop, or a particular frame may be saved for review during angioplasty. An intravenous antithrombotic agent, usually heparin, is administered before the clinician proceeds with angioplasty. The patient's activated clotting time is monitored. A 0.018-in guidewire is advanced through the 6F renal guide across the ostial right renal stenosis. A small torque device is used over the proximal segment of the guidewire for steering, while a small terminal bend is created by hand over the distal end of the guidewire before it is introduced into the guide catheter. Passage of the guidewire is monitored by using fluoroscopy and injections of small amounts of contrast agent. Occasionally, a combination of torque and forward pressure is required to cross the lesion. In addition, in tight lesions, the balloon catheter is sometimes advanced and used as a support for passage of the guidewire. A 6 X 18-mm balloon is positioned across the lesion by carefully advancing it over the guidewire. The balloon is prepared before it is loaded over the guidewire by connecting its proximal balloon port to an inflating device that contains a half-and-half solution of contrast agent and sterile saline and then by drawing negative pressure to extrude any air bubbles. The inflating device is left in negative pressure while the balloon is advanced with 1 hand and the guidewire is held with the other hand. The balloon is advanced beyond the distal end of the guide catheter, which is gently pulled back, and the balloon is straddled across the stenosed segment. A small amount of contrast agent is injected to confirm proper positioning of the balloon. The balloon is inflated by increasing the pressure with the inflation device to several atmospheres of pressure (usually 4-8 bars). The mixed solution of contrast agent and saline in the inflation device gradually moves into the balloon. As the balloon expands, it becomes visible under fluoroscopy, as shown. The balloon is held up for several seconds to apply circumferential pressure on the stenosed arterial segment and then deflated and gradually pulled back into the guide catheter. Angiogram obtained after percutaneous transluminal angioplasty and after the balloon catheter is removed but while the guidewire is still retained shows increased luminal diameter at the stenotic segment. However, the segment appears to be at least 50% narrowed. Flow into the renal artery from the aorta is increased. The vascular wall shows no clear dissection. No filling defect (which may represent clot) is visible. Distal flow into the branches of the right renal artery is brisk, with good tissue flush. A stent-balloon catheter is prepared in a manner similar to the balloon catheter; however, before it is inserted into the guide catheter, no negative pressure is created. The stent-balloon catheter is then advanced over the guidewire through the guide catheter beyond distal opening and across the lesion. The stent is positioned over the lesion by confirming its placement with the injection of a small amount of contrast material through the guide. The guide catheter is pulled back on the wire a little to allow the proximal edge of the stent to be slightly in the aorta.Before the stent balloon is inflated, the guide catheter is pushed upward to straighten the stent and wire in the proximal portion of the renal artery. The stent is then deployed by first creating negative pressure in the stent balloon and then by inflating it by injecting the contrast agent–saline solution through the inflation device. The stent is left inflated for several seconds at 5-10 bars of pressure. The balloon is then deflated and withdrawn while the guidewire is retained across the lesion, and the guide catheter is slightly advanced into the stent. Fluoroscopic image shows the guidewire still lying across the stented segment. The stent shadow is visible in the proximal portion of the right renal artery, and it appears well expanded. Last, the guidewire is withdrawn after the absence of a flap, dissection, or filling defect is confirmed. Poststenting angiogram shows 0% residual stenosis in the proximal renal artery. The guide catheter is finally withdrawn. Preangioplasty angiogram obtained in a young woman with malignant hypertension shows tight stenosis in the middle segment of the right renal artery. Its appearance is consistent with that of fibromuscular dysplasia, for which angioplasty is the procedure of choice and for which stenting is usually not indicated. Intra-arterial nitroglycerine, 300 mcg, was given without any change in the appearance of the stenosis (which differentiates it from spasm). Fluoroscopic image shows an inflated percutaneous transluminal angioplasty (PTA) balloon in the midright renal artery over the guidewire. In this case, a Judkins right 4 (JR4) guide was used to access the right renal artery via a right femoral approach. The balloon was left inflated for several seconds, then deflated and pulled out. Additional intra-arterial nitroglycerine was infused. Angiogram obtained after percutaneous transluminal angioplasty and after the balloon catheter was removed shows a good result with residual stenosis of less than 20% at the previously stenosed site. Flow into the renal artery from the aorta is increased. The vascular wall shows no clear dissection. No filling defect (which may represent clot) is visible. Distal flow into the branches of the right renal artery is brisk, with good tissue flush.

Complications of PTRA

The rate of restenosis in patients with atheromatous disease has been reported to be 19% after 9 months and 35% if the lesion is ostial. The latter rate may be an underestimate.

In the randomized study by Weibull,^[27] the 1-year rate of restenosis was 25%. Losinno et al reported a 5-year patency rate of 82%, though this percentage was based on an incomplete sample of patients.

Other complications of angioplasty include hematoma at the puncture site; azotemia, caused by the dye load; and cholesterol emboli. These complications tend to be more common in old patients with diffuse atheromatous disease than in others. When PTA is performed in patients with elevated creatinine levels, alternative contrast agents such as carbon dioxide and gadolinium-based contrast agents may be used to minimize the risk of azotemia as a complication of renal angioplasty. Findings from early clinical experience suggest that distal protection devices that are used during stenting of carotid arteries may effectively filter debris produced during renal angioplasty and stenting, preventing renal failure.

However, gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Systemic Fibrosis.

NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. For more information, see the FDA Drug Warning or this article on Medscape.

Dissection or occlusion of the renal artery may also occur, but this is rare. When this complication occurs, renal stenting may restore renal blood flow. Acute pulmonary edema as a complication of angioplasty has been reported in a patient with bilateral RAS.

In 1 large series, the 30-day mortality rate was 2.2%; all deaths occurred in patients with atheroma.

Table 4. Natural History: Progression of Medically Treated RAS^[28] (Open Table in a new window)

Clinical success rates

Several published series report clinical results obtained with angioplasty.

Fibromuscular dysplasia (FMD)

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 y after angioplasty) often show no trace of stenosis.

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 with both surgery and angioplasty is relatively high; for these patients, medical therapy may be preferred. The common indications for renal stenting include ostial stenosis, flow-limiting dissection of the renal artery after PTA, persistent significant gradient after PTA, and restenosis after balloon angioplasty. Short balloon-expandable stents are usually used for renal stenting.

Clinical outcomes

Early decrease in BP

In patients in whom PTRA is technically successful, a prompt decrease in BP is usually observed. 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 an improvement or cure of the 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.

Table 1. Success Rates of PTRA in RAS Caused by Atherosclerosis (80% of RAS) and FMD (20% of RAS)^{[29, 30]} (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.

Effect of BP 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 generally agree 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 1 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 stresses 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 for those in whom even PTRA is considered too risky, medical treatment permits the same degree of BP control achievable with dilation. Indeed, the 3 major studies that compared the effects of PTRA and medical treatment in patients with ARAS showed that the BP reductions obtained with the 2 approaches were similar. The only advantage for patients treated with PTRA was diminution of their drug regimen.

Table 2. Success Rates of PTRA in RAS Caused by Atherosclerosis (80% of RAS)^{[31, 32, 27]} (Open Table in a new window)

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 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, no evidence supports the theory that PTRA improves renal function in patients with ARAS.

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. The multicenter trial included 140 patients with creatinine clearance less than 80 mL/min per 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 renal artery stenosis by noninvasive imaging was inaccurate, and stenting was in fact not indicated. 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 2 procedure-related deaths.^[33]

Apparently, even for preserving renal function, PTRA should be performed only in patients who have been rigorously selected. Patients who might benefit from PTRA should be evaluated to the same extent as those chosen for a possible antihypertensive effect.

Table 3. Effect of Renal Stenting on Serum Creatinine Level^[30] (Open Table in a new window)

Markers of the 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 2 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.^{[34, 35, 36, 37, 38]}