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. (See the images below.)
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; medicines may cause undesirable adverse effects; and patients may be noncompliant. 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 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 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, Complications). 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. [13, 14, 15]
Etiology of renal artery stenosis
RAS has multiple causes, but most lesions are the result of atherosclerosis. FMD is the second most common etiology.  (See the image below.)
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 
RAS is found in 33% of patients with coronary artery disease (CAD)
About 18% of patients with CAD have stenoses of greater than 50% 
Both CAD and renal insufficiency are independent predictors for RAS
The incidence of bilateral RAS is approximately 46% 
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 (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  :
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
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 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 less than 3 mg/dL, or (4) acute renal failure with preserved renal size and echogenicity on ultrasonography
Other expanding indications include the following:
Congestive heart failure (CHF)
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 
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  )
High-grade RAS in patients undergoing infrarenal abdominal aortic aneurysm repair 
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 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)
Clinical success rates
Several published series report clinical results obtained with angioplasty. (See Table 1 below.)
|Outcome||ARAS, %||RAS due to FMD, %|
*Ostial location is an independent predictor of poor outcome. Clinical success rates are 54% at 3 years, with high restenosis rates.
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.
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 the following:
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.
Early decrease in blood pressure
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 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 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 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 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 those in whom even PTRA is considered too risky, medical treatment permits the same degree of BP control achievable with dilation. Indeed, the three major studies that compared 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). The only advantage for patients treated with PTRA was diminution of their drug regimen.
|Intervention||Success Rate, %||Restenosis Rate, %|
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, no evidence supports the theory that PTRA improves renal function in patients with ARAS. (See Table 3 below.)
|Decrease in GFR||37|
|Increase in creatinine level||20|
|Decrease in renal size||35|
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 two procedure-related deaths.
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. (See Table 4 below.)
|Change in Creatinine level||Rate, %|
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. [31, 32, 33, 34, 35]