Treatment of unilateral atherosclerotic renal artery stenosis

INTRODUCTION — Renal artery stenosis is a relatively common finding in older patients with hypertension. The vast majority (≥85 percent) of cases in Western societies are the result of atherosclerosis. However, renal artery stenosis is the primary cause of hypertension (ie, renovascular hypertension) only in certain settings.

In most cases of renal artery stenosis, one kidney is affected, with the main vessels to the second kidney being essentially normal, hence the designation, "unilateral" disease. Individuals with high-grade stenosis to both kidneys, or to a solitary functioning kidney thereby affecting the entire functioning kidney mass, are considered to have "bilateral" disease.

The treatment of unilateral atherosclerotic renal artery stenosis will be reviewed here. The primary concern with unilateral renal artery disease focuses on its role in raising systemic arterial pressure. Clinical clues suggesting the presence of renovascular hypertension and establishing the diagnosis of renal artery stenosis, treatment of bilateral atherosclerotic renal artery stenosis, issues related to chronic kidney disease associated with atherosclerotic renovascular disease, and diagnosis and treatment of fibromuscular disease are presented in detail elsewhere:

●(See "Evaluation of secondary hypertension".)

●(See "Establishing the diagnosis of renovascular hypertension".)

●(See "Treatment of bilateral atherosclerotic renal artery stenosis or stenosis to a solitary functioning kidney".)

●(See "Chronic kidney disease resulting from atherosclerotic renal artery stenosis".)

●(See "Clinical manifestations and diagnosis of fibromuscular dysplasia".)

●(See "Treatment of fibromuscular dysplasia of the renal arteries".)

BRIEF REVIEW OF PRESENTATION AND DIAGNOSIS

Epidemiology — While anatomic renal artery stenosis is common, the prevalence of renovascular hypertension is probably less than 1 percent in patients with mild hypertension but may be as high as 10 to 40 percent in patients with acute (even if superimposed on a preexisting elevation in blood pressure), severe, or refractory hypertension [1]. (See "Evaluation of secondary hypertension", section on 'Clinical clues for renovascular hypertension'.)

In three prospective treatment trials of patients with renal artery stenosis, the prevalence of unilateral disease (compared with bilateral disease) ranged from 53 to 80 percent [2-4]. Most patients with unilateral renal artery stenosis can achieve goal blood pressures with antihypertensive drug therapy.

Etiology — There are two major causes of unilateral renal artery stenosis:

●Atherosclerosis – Atherosclerosis primarily affects patients over the age of 45 years and usually involves the aortic orifice or the proximal main renal artery. This disorder is particularly common in patients with diffuse atherosclerosis [5] but can occur as an isolated kidney lesion. (See "Chronic kidney disease resulting from atherosclerotic renal artery stenosis".)

●Fibromuscular dysplasia – In contrast to atherosclerosis, fibromuscular dysplasia (FMD) that produces renovascular hypertension most often affects women under the age of 50 years and typically involves the distal main renal artery or the intrarenal branches. It can be seen in tandem with atherosclerotic renal artery disease and may exacerbate hemodynamic compromise [6]. (See "Clinical manifestations and diagnosis of fibromuscular dysplasia" and "Treatment of fibromuscular dysplasia of the renal arteries".)

Clinical clues — There are a number of clinical findings that suggest an increased likelihood of secondary hypertension, some of which specifically suggest the presence of renovascular disease. These findings are used clinically to determine which patients should be evaluated for renovascular disease (table 1). Some of these clues are relatively specific for the presence of renovascular disease, and some help to identify those patients who are more likely to benefit from intervention. These clinical clues, as well as the indications for testing to establish the diagnosis of renal artery stenosis, are presented in detail in other topics. (See "Evaluation of secondary hypertension" and "Establishing the diagnosis of renovascular hypertension", section on 'Indications for testing'.)

Advances in contrast imaging (computed tomography [CT] and magnetic resonance [MR] angiography) and Doppler ultrasound have led to the identification of renal arterial stenoses as an "incidental finding" more commonly than before [7]. The absence of clinical clues for renovascular hypertension in such patients substantially reduces the likelihood that the renal artery stenosis is responsible for hypertension, if present, and also reduces the likelihood of benefit from percutaneous or surgical intervention [8,9]. (See "Establishing the diagnosis of renovascular hypertension", section on 'Incidental lesions'.)

Diagnosis — The diagnosis of unilateral renal artery stenosis is made by imaging studies in patients thought to be at risk. With duplex Doppler ultrasonography, a peak systolic velocity above 200 cm/sec suggests a stenosis of greater than 60 percent, although some studies indicate that a peak systolic velocity above 300 cm/sec represents a hemodynamically more important threshold. With computed tomography and MR angiography, a stenosis greater than 75 percent in one or both renal arteries, or a 50 percent stenosis with post-stenotic dilatation, suggests that the lesion may be producing hemodynamically significant reductions in renal blood flow and perfusion pressure. Such patients may therefore have renovascular hypertension. These issues are discussed in detail separately. (See "Establishing the diagnosis of renovascular hypertension".)

RISK FACTOR REDUCTION — Patients with atherosclerotic renovascular disease have a high prevalence of systemic atherosclerosis and are at increased risk for adverse cardiovascular outcomes. As a result, they are considered to have a coronary artery disease equivalent and should be treated according to current guidelines for secondary prevention of cardiovascular disease. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

TREATMENT

General approach to therapy — Once a patient who has a high probability of having renovascular hypertension (based upon clinical clues) is diagnosed with renal artery stenosis, there are three therapeutic options available:

●Medical therapy (essentially all patients)

●Percutaneous revascularization with angioplasty with or without stent placement

●Surgical revascularization or, in some cases, resection of a "pressor" kidney

We suggest the following approach in patients with unilateral atherosclerotic renal artery stenosis:

●Medical therapy for control of hypertension in all patients with unilateral renal artery stenosis. Ideally, antihypertensive therapy should include an agent that blocks the renin-angiotensin-aldosterone system, such as an angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) [10-12].

●Revascularization, usually by percutaneous angioplasty with stenting (or surgical revascularization in patients with complex anatomic lesions), is reasonable in patients with unilateral disease who have a high likelihood of benefitting from intervention. The following scenarios identify such patients:

•A short duration of blood pressure elevation prior to the diagnosis of renovascular disease, since this is the strongest clinical predictor of a fall in blood pressure after renal revascularization. The duration of blood pressure elevation after which revascularization is unlikely to be helpful is unclear. One study, however, suggested that cure with surgical revascularization was uncommon if the hypertension was present and unchanged for more than several years [13].

•Failure of optimal medical therapy to control the blood pressure.

•Intolerance to optimal medical therapy.

•Recurrent flash pulmonary edema and/or refractory heart failure.

In addition, we suggest revascularization in patients with bilateral renal artery stenosis (or unilateral stenosis to a solitary functioning kidney) who have progressive kidney function impairment that is thought to be a result of the stenosis. This issue is discussed separately. (See "Treatment of bilateral atherosclerotic renal artery stenosis or stenosis to a solitary functioning kidney", section on 'Treatment' and "Chronic kidney disease resulting from atherosclerotic renal artery stenosis".)

Our suggestions presented above are broadly consistent with the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on peripheral artery disease [14], a consensus statement from the Society for Cardiovascular Angiography and Intervention (SCAI) [15], the 2017 ACC/AHA hypertension guidelines [10], and the 2022 Kidney Disease: Improving Global Outcomes (KDIGO) recommendations [12].

The above suggestions apply to unilateral atherosclerotic renal artery stenosis. Our suggestions for treatment of bilateral atherosclerotic renal artery stenosis and fibromuscular dysplasia (FMD) are presented elsewhere. (See "Treatment of bilateral atherosclerotic renal artery stenosis or stenosis to a solitary functioning kidney" and "Treatment of fibromuscular dysplasia of the renal arteries".)

Revascularization versus medical therapy alone — Revascularization using percutaneous transluminal renal angioplasty (PTRA) with or without stent in combination with medical therapy has been compared with medical therapy alone in eight randomized trials that included patients with unilateral atherosclerotic renal artery stenosis [2-4,9,16-20]. A meta-analysis of these trials found no benefit from PTRA on mortality, end-stage kidney disease (ESKD), major cardiovascular events, and only modest effects on blood pressure control [21].

The largest of the trials was the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, which included 947 patients (80 percent had unilateral disease) who met the following two criteria [2]:

●Unilateral or bilateral atherosclerotic renal artery stenosis. The definition of stenosis varied with the imaging study that was used:

•Luminal narrowing >60 percent if diagnosed with conventional angiography

•A peak systolic velocity >300 cm/second if diagnosed by duplex Doppler ultrasonography

•Luminal narrowing >80 percent if diagnosed with magnetic resonance angiography or computerized tomography angiography (or >70 percent with additional evidence of kidney ischemia)

●Systolic hypertension despite two or more antihypertensive medications and/or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² that was presumably due to the stenosis.

All patients received antiplatelet therapy plus standardized medical treatments for hypertension, hyperlipidemia, and hyperglycemia, and were then randomly assigned to revascularization (ie, PTRA with stenting) or to no revascularization. All patients were provided an angiotensin receptor blocking agent as part of the trial (candesartan). After a median of 3.6 years, the following findings were noted [2]:

●Revascularization had no additional effect on the primary outcome (a composite of cardiovascular or kidney death, stroke, myocardial infarction, hospitalization for heart failure, a reduction in eGFR by more than 30 percent, or end-stage kidney disease) as compared with medical therapy alone (35.1 versus 35.8 percent). Similarly, revascularization had no effect on any of the individual components of the primary outcome.

●Patients assigned revascularization plus medical therapy had a mean systolic blood pressure throughout the trial that was approximately 2 mmHg lower than those assigned medical therapy alone.

●Serious adverse events associated with revascularization were uncommon. The most frequent serious complication was renal artery dissection, which occurred in 11 revascularized patients (2.2 percent).

Periprocedural complications associated with PTRA vary. In a meta-analysis of randomized trials and observational studies [21], for example, procedure-related deaths occurred in 0.7 percent of patients, acute kidney injury occurred in 2.8 percent, and renal artery perforations or dissections also occurred in 2.8 percent. A total of 7.1 percent developed one or more major periprocedural complications, and, as noted above, there was no important clinical benefit from PTRA with or without stenting.

However, two major criticisms are applicable to each of the eight randomized trials [22-25]:

●Considerable selection bias – For the most part, the patients enrolled in these trials did not meet the criteria listed above for selecting patients likely to benefit from intervention (eg, short duration of blood pressure elevation, hypertension resistant to medical therapy, recurrent flash pulmonary edema):

•In CORAL, for example, patients who were hospitalized for heart failure within 30 days of screening for the trial were excluded, thereby limiting the number of trial participants with recurrent flash pulmonary edema [2]. In addition, the mean number of antihypertensive medications used by CORAL participants at baseline was 2.1, indicating that many had not failed optimal medical therapy, and more than 25 percent had controlled blood pressure upon entry into the trial. The mortality and event rates in CORAL were also lower than in most previous registries, suggesting that many high-risk patients were not enrolled.

•In ASTRAL, many patients had stenoses that were probably not clinically significant (50 to 70 percent), and patients were excluded if their primary doctors felt that they "definitely" needed revascularization [3].

●Results of the trials differ substantially from observational reports of "high-risk" subsets – For the most part, patients selected by their treating clinicians to undergo revascularization have derived greater benefit from revascularization than did patients enrolled in the trials who were randomly assigned to revascularization [24,26-28]. This finding may be related to the selection bias associated with each of the trials, as mentioned above. The following examples are illustrative:

•In a prospective cohort, 467 patients with renal artery stenosis were treated with either revascularization or medical therapy alone according to patient and clinician preferences [26]. Of these, 37 (7.8 percent) had flash pulmonary edema, 116 (24.3 percent) had resistant hypertension, 46 (9.7 percent) had progressive kidney function impairment (defined as a rise in serum creatinine of 20 percent or more or an absolute increase of 1.14 mg/dL [100 micromol/L] or more during the preceding six months), and 31 (6.6 percent) had both resistant hypertension and progressive kidney function impairment. Revascularization was independently associated with the following benefits at four years: a significantly lower risk of death in patients with flash pulmonary edema (58 versus 76 percent) and with both resistant hypertension and progressive kidney function impairment (9 versus 65 percent); and a significantly lower risk of cardiovascular events among patients with both resistant hypertension and progressive kidney function impairment (27 versus 60 percent). By contrast, revascularization was not associated with such benefits in patients without these risk factors.

•An observational study compared the outcomes of 347 patients with renal artery stenosis treated with medical therapy alone with 89 patients treated with PTRA [24]. Of these 89 patients, most underwent revascularization because of specific indications (eg, refractory hypertension, flash pulmonary edema, intolerance to angiotensin inhibition), whereas the remainder had PTRA because they were enrolled in a randomized trial. The patients who underwent revascularization had more comorbidity at baseline than patients who received medical therapy alone. Despite this, patients who had revascularization had significantly lower rates of mortality and kidney disease progression after multivariable analysis.

•In another study, 39 patients who underwent PTRA with stent for refractory heart failure were followed for a mean of 21 months [27]. After stenting, there were significant declines in blood pressure (from 174/85 to 148/72 mmHg), New York Heart Association (NYHA) functional class (from 2.9 to 1.6), and number of annual hospitalizations for heart failure (from 2.4 to 0.3 per year). In addition, the mean serum creatinine significantly decreased (from 3.2 to 2.6 mg/dL).

Thus, for patients with unilateral atherosclerotic renal artery stenosis who have characteristics similar to those enrolled in the trials, there are high-quality data that PTRA provides no additional benefit to medical therapy and increases the risk of adverse events. By contrast, for patients who have specific characteristics (described immediately below), there are lesser-quality data that PTRA plus medical therapy is superior to medical therapy alone [29].

The specific characteristics that identify patients with unilateral stenosis who may benefit from revascularization include:

●A short duration of blood pressure elevation prior to the diagnosis of renovascular disease (less than two to five years)

●Failure of optimal medical therapy to control the blood pressure

●Intolerance to optimal medical therapy

●Recurrent flash pulmonary edema and/or refractory heart failure

Overview of therapeutic options — There are three therapeutic options available:

●Medical therapy

●Percutaneous angioplasty with or without stent placement

●Surgical revascularization or, in some cases, resection of a "pressor" kidney

Medical therapy — The availability of ACE inhibitors and ARBs has markedly improved the ability to control the blood pressure in patients with renovascular disease [30-32]. Population-based observational studies indicate that including renin-angiotensin system blockade for individuals with renal artery stenosis is associated with reduced mortality [33]. If goal blood pressure is not reached with angiotensin inhibition alone, other antihypertensive drugs, such as a thiazide diuretic (preferably chlorthalidone or indapamide), a long-acting calcium channel blocker, a mineralocorticoid receptor antagonist, or a beta blocker, should be added as necessary [8,30]. (See "Choice of drug therapy in primary (essential) hypertension".)

There are, however, a number of potential concerns with medical treatment:

●Progression of the stenosis and vascular occlusion

●Impaired kidney function with angiotensin inhibition

●Long-term ischemic damage in the stenotic kidney

Progression of stenosis — Concerns with using medical therapy alone to treat patients with renal artery stenosis include progression of the stenotic lesion and/or development of stenosis in the contralateral kidney. Variable rates of progression have been described:

●A retrospective study of 85 patients with atherosclerotic renal artery stenosis who underwent serial angiograms found that stenotic lesions progressed in 37 patients at four years (44 percent) and occluded in 14 patients (16 percent) [34].

●Another study identified 1189 patients with various degrees of renal artery stenosis who had repeated renal arteriograms separated by an average of 2.6 years [35]. Progression of stenosis occurred in 11 percent of patients and did not depend upon the baseline severity of stenosis.

●A prospective cohort study of 170 patients who underwent serial duplex ultrasonography found that the rate of progression of stenosis was 35 percent at three years and 52 percent at five years [36]. Progression was more likely to occur in patients who had more severe stenoses at baseline: the three-year incidence of progression was 49 percent if the baseline stenosis was 60 percent or greater and 28 percent if the baseline stenosis was less than 60 percent.

Progression to end-stage kidney disease (ESKD) is rare in patients with unilateral disease, and unilateral occlusion may correspond with only a small change in serum creatinine. Among more than 300 patients with atherosclerotic renal artery stenosis, for example, progression to ESKD over a 4- to 10-year period occurred in only one patient, even though some patients had an initial stenotic lesion of 70 percent or more [7,37]. No mention was made concerning radiographic progression of these lesions or the incidence and complications of hypertension.

Although ESKD is uncommon in these patients, progressive kidney disease of lesser severity commonly occurs. In two randomized trials, progression of kidney disease (defined as a fall in glomerular filtration rate [GFR] by 20 percent or a doubling of serum creatinine) in patients assigned to medical therapy developed in 16 to 22 percent at two to five years [3,4]. As with any form of vascular disease, decisions regarding follow-up imaging will depend in part upon the likelihood of acting on that information.

Progression is more likely and carries more clinical import in patients with bilateral renal artery stenosis or stenosis of a solitary functioning kidney [38]. Patients with atherosclerotic renovascular disease have an increased rate of extrarenal atherosclerosis and as much as a two- to fourfold increase for cardiovascular events [39].

The issues of progression of atherosclerotic renal artery stenosis and increased cardiovascular risk are discussed in detail separately. (See "Chronic kidney disease resulting from atherosclerotic renal artery stenosis".)

In patients with FMD, the likelihood of progression is lower, total occlusion is rare, and there is no association with systemic atherosclerosis. (See "Clinical manifestations and diagnosis of fibromuscular dysplasia", section on 'Monitoring disease progression'.)

Impaired kidney function with angiotensin inhibition — The high angiotensin II levels induced by reduced renal blood flow act to preserve the GFR by preferentially increasing the resistance at the efferent (postcapillary) glomerular arteriole. Inhibiting this compensatory response with an ACE inhibitor or ARB can lower GFR in the post-stenotic kidney, even though the associated decrease in renal vascular resistance may preserve renal blood flow [40,41]. A more complete discussion of the role of angiotensin II in the regulation of GFR in renovascular hypertension is presented separately. (See "Renal effects of ACE inhibitors in hypertension".)

Studies in humans with unilateral renal artery stenosis demonstrate that, despite the reduction in filtration in the stenotic kidney, the total GFR is usually maintained due to a roughly equivalent rise in filtration in the contralateral kidney following the removal of angiotensin II-induced vasoconstriction [42]. A modest elevation in the serum creatinine concentration can occur in selected cases, a change that may be due to intrarenal vascular disease (nephrosclerosis) in the contralateral kidney that has been exposed to high systemic pressures [41,43]. A more significant reduction in kidney function has been described in older adult patients with a baseline GFR less than 50 mL/min per 1.73 m² [44].

A decline in GFR is less common with other antihypertensive agents, which do not preferentially decrease the resistance at the efferent arteriole. However, when vascular stenosis reaches a "critical" level, reduction in perfusion pressure with any antihypertensive agent can lower GFR, which will be clinically evident in patients who have bilateral disease (figure 1) [45].

Loss of functional kidney mass in the stenotic kidney — An additional concern when medical therapy alone is used to treat unilateral atherosclerotic renal artery stenosis is the long-term effect of reduced blood flow and perfusion pressures on the stenotic kidney [46]. The kidney receives an abundant blood supply in its role as a filtering organ and can adapt to moderately reduced blood flow without developing overt tissue ischemia [47]. Nonetheless, sufficient reduction of blood flow eventually produces cortical hypoxia, microvascular rarefaction, and development of interstitial inflammation, tubular atrophy, and irreversible fibrosis [48-50].

It has been suggested that these changes are more likely to occur with angiotensin inhibition [41], but this finding has not been uniform:

●One study evaluated 122 patients with unilateral or bilateral disease in whom duplex ultrasonography was performed every six months [51]. An enhanced risk of loss of mass in the ischemic kidney was associated with a greater degree of stenosis and a higher blood pressure (systolic pressure greater than 180 mmHg) but not with the use of ACE inhibitors. At two years, the incidence of kidney atrophy, defined as a reduction in kidney length of greater than 1 cm, was 5.5, 11.7, and 20.8 percent in those with a baseline renal artery disease categorized as normal, less than 60 percent stenosis, and greater than 60 percent stenosis, respectively (p = 0.009).

●A second report performed serial duplex Doppler ultrasonographic studies in 54 patients with at least a 60 percent stenosis in at least one renal artery to assess both the degree of renal artery stenosis and kidney size [52]. The type of therapy was not described. At one year, more than a 1.0 cm decrease in kidney size occurred in 13 percent of patients with unilateral disease versus 43 percent with bilateral stenoses. Cumulative progression to total occlusion was 2.1 percent at one year and 5 percent at two years.

Thus, persistent severe stenosis carries the risk of long-term loss of kidney mass. The functional consequences are greater in patients with bilateral disease in whom progressive kidney failure can occur. (See "Treatment of bilateral atherosclerotic renal artery stenosis or stenosis to a solitary functioning kidney" and "Chronic kidney disease resulting from atherosclerotic renal artery stenosis".)

Percutaneous transluminal renal angioplasty — Percutaneous transluminal renal angioplasty (PTRA) provides a nonsurgical method to open stenotic renal arteries (image 1A-B). Based upon various studies, the major conclusions regarding PTRA include the following:

●The maximum antihypertensive response is generally observed at 48 hours after the procedure [53]. Blood pressure levels and antihypertensive drug requirements often change over subsequent weeks. A final determination of the blood pressure response to PTRA should not be made during this interval. Certain hemodynamic measurements obtained during angiography may predict a successful blood pressure response at 3 to 12 months following PTRA [54]. As examples, a systolic gradient across the stenosis of greater than 20 mmHg after intraarterial infusion of papaverine had a 90 percent positive predictive value for durable blood pressure control in one study; in another study, a mean blood pressure gradient greater than 22 mmHg under similar conditions had a 79 percent positive predictive value.

●The technical success rate varies with the site of the lesion. In general, the most amenable lesions to angioplasty are those producing incomplete occlusion in the main renal artery. Total occlusions and ostial lesions (which also involve the aorta) generally do not respond well to angioplasty alone due to elastic recoil. Most atherosclerotic lesions are now treated with primary stenting to avoid rapid development of restenosis. (See 'Stent placement' below.)

●Among patients with unilateral atherosclerotic disease, PTRA alone results in normalization of blood pressure (ie, removal of antihypertensive drug therapy) in 8 to 20 percent, improvement in 50 to 60 percent, a failure rate of approximately 20 to 30 percent, and a restenosis rate of 8 to 30 percent at two years [55,56]. Results were somewhat better with unilateral fibromuscular disease [57]. The results are less consistent for patients with bilateral disease or chronic hypertension compared with patients who have an acute elevation in blood pressure [1].

Stent placement — In patients undergoing PTRA for treatment of atherosclerotic renal artery stenosis, we suggest stent placement. In a randomized trial, PTRA alone was compared with PTRA plus stent placement in 85 hypertensive patients with ostial atherosclerotic renal artery stenosis (51 percent of which were unilateral); all patients were hypertensive (>160/95 mmHg, mean 186/103 mmHg), the mean degree of stenosis was 76 percent, and the mean serum creatinine was 1.6 mg/dL (139 micromol/L) [58]. The patients were randomly assigned to one or the other intervention.

PTRA plus stenting was associated with the following significant benefits compared with PTRA alone:

●A higher initial primary success rate, defined as less than 50 percent stenosis (88 versus 57 percent).

●At six months, a higher patency rate (75 versus 29 percent) and a lower restenosis rate (14 versus 48 percent).

●Twelve patients assigned to PTRA alone underwent stenting because of treatment failure within six months. These patients had a similar blood pressure response as those initially treated with stenting.

●The rate of normalization or improvement in blood pressure control was not significantly higher in the stenting group on intention to treat analysis (58 versus 49 percent), but this finding was influenced by the inclusion of 12 patients originally assigned to PTRA who underwent secondary stenting.

●Most patients had stable kidney function.

In addition, a number of prospective studies indicate that PTRA with stent placement compared with PTRA alone decreases the rate of restenosis [56,58-61] and is more effective in terms of improving blood pressure and stabilizing or improving kidney function [56,59-63].

Our suggestion that a stent be placed in patients undergoing PTRA for treatment of atherosclerotic renal artery stenosis is consistent with the 2013 ACC/AHA guidelines on peripheral artery disease [14]. PTRA without stent placement is rarely performed unless the anatomy precludes stenting.

Procedural complications — A variety of procedural complications can occur with angioplasty with or without stenting. Most are relatively minor and include puncture site hematoma and renal artery dissection. However, serious problems can arise, including renal artery thrombosis or perforation (sometimes requiring surgery) and acute kidney injury due to atheroembolic disease (which may be irreversible) or to a reaction to the radiocontrast agent (which is usually reversible). These issues are discussed in detail elsewhere. (See "Treatment of bilateral atherosclerotic renal artery stenosis or stenosis to a solitary functioning kidney", section on 'Procedural complications'.)

Restenosis rates range between 11 and 17 percent and may be detected as a rise in blood pressure requiring more intensive therapy [64]. Stenting injures the vascular endothelium, which may predispose to restenosis. Prospective follow-up of patients who have had a stent suggests that restenosis develops in 11 to 39 percent of cases during the first one to two years [60,64-66], although it can develop at any time. Symptomatic stenosis leading to a rise in blood pressure or a fall in GFR are less common and are reported in 10 to 20 percent of patients [67]. Thus, the routine follow-up of patients who have had a renal artery stent should include serial measurements of blood pressure and estimation of GFR. Some experts also suggest a post-stent duplex ultrasound (at two weeks) with repeated examinations on a quarterly basis, although few data are available to support this approach [65]. Patients who develop an increase in pressure or reduced GFR after stenting should undergo duplex ultrasonography to identify restenosis [68,69]. Retreatment with angioplasty with or without repeat stenting can be attempted, but the restenosis rate after repeat angioplasty is increased. Surgical reconstruction may be pursued in patients with recurrent episodes of restenosis and loss of kidney function.

Split kidney function — Since total GFR is usually maintained in patients with unilateral renal artery stenosis, another measure of success after PTRA may be the relative loss of lateralization of kidney function. In a prospective study, 32 hypertensive patients with unilateral renal artery stenosis (≥60 percent stenosis on angiography) and normal global kidney function underwent PTRA, with follow-up in part consisting of split kidney function assessment, including single kidney and global GFR measurements [70]. At six months postprocedure, the GFR significantly increased in the stenotic kidneys (31 to 41 mL/min per 1.73 m2) and fell in the nonstenotic kidneys (59 to 53 mL/min per 1.73 m2). It is unclear whether these findings are associated with long-term kidney benefits.

Surgery — Surgical renal revascularization has been performed less commonly since the widespread application of effective antihypertensive drug therapy and endovascular stents in the mid-1990s [71]. We agree with the ACC/AHA guidelines that, among patients who have an indication for renal artery revascularization, surgery is preferred only for selected patients who have complex anatomic lesions [72,73]:

●Multiple small renal arteries or restenosis after failed PTRA and stenting.

●Early primary branching of the main renal artery.

●Requirement for aortic reconstruction near the renal arteries for other indications, such as aneurysm repair or severe aortoiliac occlusive disease.

●In order to avoid manipulation of a highly diseased aorta or failed endovascular stents (using specific surgical techniques, including splenorenal, ileorenal, or hepatorenal bypass procedures).

Surgical therapy in unilateral atherosclerotic renal artery stenosis consists of bypassing the stenotic segment or of removing a small atrophic kidney with nearly complete arterial occlusion. Surgery is equally or more effective than PTRA in the treatment of atherosclerotic disease, with cure of or improvement in the hypertension occurring in 80 to 95 percent of patients [74]. Cure of hypertension after surgery is most likely in patients who have been hypertensive for less than five years [13]. In this study, a lack of complete response was usually associated with one of two factors: the presence of underlying primary hypertension (formerly called "essential" hypertension), upon which renovascular disease has been superimposed, or the development of intrarenal vascular disease due to exposure of the contralateral kidney to the elevated blood pressure.

In a randomized trial, 58 patients with unilateral atherosclerotic renal artery stenosis were assigned to surgery or PTRA without stenting [75]. Surgery was associated with a higher primary success rate (97 versus 83 percent) and a lower incidence of restenosis at two years (4 versus 25 percent). However, the outcomes were similar in the two groups since almost all patients with restenosis could be successfully treated with repeat PTRA.

The mortality rate associated with surgery for atherosclerotic renal artery stenosis varies with the severity of the extrarenal vascular disease, the degree of surgery required, and the experience of the local surgical team. Overall mortality rates below 2.5 percent have been reported from some of the most experienced centers [74,76,77]. The outcome is best for younger patients (less than 65 years old) who do not have symptomatic coronary or cerebrovascular disease and who require only renal artery surgery. Most operative deaths occur in patients with diffuse atherosclerosis who also have heart failure and/or moderate to advanced chronic kidney disease [70].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hypertension in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Renovascular hypertension (The Basics)")

SUMMARY AND RECOMMENDATIONS

●In most cases of renal artery stenosis, one kidney is affected with the second kidney being essentially normal, hence the designation, "unilateral" disease. Individuals with high-grade stenosis to both kidneys, or to a solitary functioning kidney thereby affecting the entire functioning kidney mass, are considered to have "bilateral" disease. (See 'Introduction' above.)

●There are two major causes of unilateral renal artery stenosis (see 'Etiology' above):

•Atherosclerosis, which primarily affects patients (particularly men) over the age of 45 years and usually involves the aortic orifice or the proximal main renal artery. This disorder is particularly common in patients with diffuse atherosclerosis.

•Fibromuscular dysplasia (FMD), which most often affects women under the age of 50 years and typically involves the distal main renal artery or the intrarenal branches. Fibromuscular disease is discussed in other topics. (See "Clinical manifestations and diagnosis of fibromuscular dysplasia" and "Treatment of fibromuscular dysplasia of the renal arteries".)

●There are a number of clinical findings that suggest an increased likelihood of secondary hypertension, some of which specifically suggest the presence of renovascular disease (table 1). These clinical clues, the indications for testing to establish the diagnosis of renal artery stenosis, and the imaging studies used to establish the diagnosis are presented in detail in other topics. (See "Evaluation of secondary hypertension" and "Establishing the diagnosis of renovascular hypertension", section on 'Indications for testing' and "Establishing the diagnosis of renovascular hypertension", section on 'Diagnostic test options'.)

●Patients with atherosclerotic renovascular disease have a high prevalence of systemic atherosclerosis and are at increased risk for adverse cardiovascular outcomes. As a result, they are considered to have a coronary artery disease equivalent and should be treated according to current guidelines for secondary prevention of cardiovascular disease. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

●Patients with unilateral renal artery stenosis who are hypertensive should receive antihypertensive therapy. The data and specific recommendations are presented elsewhere. (See "Goal blood pressure in adults with hypertension".)

●Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are effective in patients with renovascular disease; additional medications are frequently required. Potential concerns with the use of medical therapy without revascularization include progression of the stenosis, impaired kidney function with angiotensin inhibition, and long-term ischemic damage of the stenotic kidney. (See 'Medical therapy' above.)

●For patients with unilateral renal artery stenosis who meet one or more of the following four criteria, we suggest revascularization rather than medical therapy alone; revascularization is usually achieved by percutaneous angioplasty with stenting (or surgical revascularization in patients with complex anatomic lesions) (see 'Revascularization versus medical therapy alone' above) (Grade 2C):

•A short duration of blood pressure elevation prior to the diagnosis of renovascular disease, since this is the strongest clinical predictor of a fall in blood pressure after renal revascularization

•Failure of optimal medical therapy to control the blood pressure

•Intolerance to optimal medical therapy

•Recurrent flash pulmonary edema and/or refractory heart failure

●For patients with unilateral renal artery stenosis who do not meet one of the four criteria just listed, we suggest not revascularizing and instead treating with medical therapy alone (Grade 2B). (See 'Revascularization versus medical therapy alone' above.)

●In patients undergoing percutaneous transluminal renal angioplasty (PTRA) for treatment of atherosclerotic renal artery stenosis, we suggest stent placement unless the anatomy precludes stenting (Grade 2B). (See 'Percutaneous transluminal renal angioplasty' above.)

●Among patients who have an indication for renal artery revascularization, surgery is only preferred for selected patients who have complex anatomic lesions (see 'Surgery' above):

•Multiple small renal arteries or multiple prior failed PTRA or stent procedures

•Early primary branching of the main renal artery

•Requirement for aortic reconstruction near the renal arteries for other indications, such as aneurysm repair or severe aortoiliac occlusive disease

•In order to avoid manipulation of a highly diseased aorta or failed endovascular stents (using specific surgical techniques, including splenorenal, ileorenal, or hepatorenal bypass procedures)