Renal Artery Stenosis Treatment & Management

All patients with significant (> 80%) bilateral stenosis or stenosis in a solitary functioning kidney are candidates for revascularization, regardless of whether they have kidney insufficiency. When kidney insufficiency is present, patients with unilateral stenosis are also possible candidates for revascularization. The criteria are slightly different depending on the presence or absence of kidney insufficiency.

When kidney function is normal or nearly normal, specialists recommend revascularization for prevention of kidney insufficiency if the patient meets the following criteria:

• The degree of stenosis is more than 80-85%.
• The degree of stenosis is 50-80%, and captopril-enhanced scintigraphy demonstrates an activation of intrarenal renal artery stenosis.

Conversely, physicians can choose observation instead of revascularization (serial control every 6 mo with duplex scanning, accurate correction of dyslipidemia, use of drugs that block platelet aggregation) when the patient meets the following criteria:

• Stenosis is 50-80% and scintigraphy findings are negative.
• The degree of stenosis is less than 50%.

When kidney insufficiency is present and the objective is recovery of kidney function together with prevention of further kidney function impairment, the prerequisites for revascularization are as follows:

• The serum creatinine level is lower than 4 mg/dL, or
• The serum creatinine level is higher than 4 mg/dL but with a possible recent renal artery thrombosis.

When either of those conditions is satisfied, the authors propose revascularization if the following apply:

• The degree of stenosis is more than 80%.
• The serum creatinine level rises after administration of angiotensin-converting enzyme (ACE) inhibitors.
• The degree of stenosis is 50-80% and scintigraphy findings are positive.

Restrict conservative treatment in patients with an established diagnosis of ischemic renal disease to those with absolute contraindications to surgery or angioplasty or to patients who are likely to succumb to other comorbid conditions before advancing to end-stage renal disease because of ischemic renal disease. Clinicians must rely on pharmacologic agents (eg, combination of calcium channel blockers to control blood pressure and optimize renal perfusion), accepting the high probability of deterioration in kidney function and shortened survival.

In 1962, Morris et al compiled the first report on a surgical treatment for occlusion of the renal arteries. ^[35] They described eight patients with kidney failure who underwent revascularization. Six of these patients returned to essentially normal kidney function.

Reports from retrospective studies clearly document that surgical revascularization can improve renal function in patients with ischemic nephropathy. In 1993, Rimmer and Gennari reported postoperative improvement (ie, 20% decrease in serum creatinine concentration) in more than half the patients in nine studies. ^[36]  A long-term study (median follow-up, 10.6 years) of open surgical renal artery reconstruction that included 31 patients with stenosis reported low mortality, fairly low morbidity, and excellent durability and recommended that open surgery remain an option for patients with complex renal artery disease. ^[37]

Bypass procedures include aortorenal, hepatorenal, splenorenal, and ileorenal conduits constructed with autologous saphenous veins, autologous arteries, or prosthetic material. For atherosclerotic disease, surgeons can also perform atherectomy to improve renal blood flow. In persons with nonatheromatous renal artery disease, surgeons can reconstruct the renal arteries ex vivo and then can reimplant the revascularized kidney. Reilly and coworkers reported an operative mortality rate of only 6% and immediate improvement in the serum creatinine level of 32% of surgical bypass procedures in 35 patients with solitary kidneys. ^[38]

Subsequent studies reported more consistent success. The largest series suggests that the glomerular filtration rate (GFR) improved postoperatively in 49-80% of patients with underlying kidney failure.  

Guidelines from the American Heart Association/American College of Cardiology and the European Society of Cardiology include recommendations for the use of peripheral revascularization and surgical revascularization. See Guidelines.

Revascularization

One unresolved issue is how to determine whether revascularization will salvage kidney function when the renal artery is totally occluded. Features that may predict successful restoration of kidney function include the following:

• Collateral circulation and nephrogram on angiography findings
• Kidney length longer than 9 cm
• Lateralization of renin secretion
• Differential concentration of urine on split-function study results
• Spontaneous back-bleeding findings after arteriotomy during surgery
• Viable nephrons on biopsy tissue examination

Specialists suggest nephrectomy as a modality of treatment in persons with unilateral renovascular disease. However, in one study that involved 95 hypertensive patients and 100 kidneys with chronic atherosclerotic renal artery occlusion, nephrectomy versus revascularization provided equivalent estimated survival and blood pressure benefits, but in patients treated for unilateral disease, improvement in kidney function was observed only after revascularization. Moreover, improved kidney function was significantly and independently associated with improved survival. Those authors reserved nephrectomy for a surgically unreconstructible renal artery to a poorly functioning kidney. ^[39]

Angioplasty and stenting

Angioplasty is effective for treating renovascular hypertension associated with atheromatous lesions. Indicative of this is the decreased rate of referrals for surgical renovascularization of atheromatous renovascular hypertensive nephropathy by the early 1980s (from 41% to 26%). In practical terms, angioplasty can usually limit hospitalization, avoid general anesthesia, and minimize tissue trauma.

In 1987, Ziegelbaum et al compared the outcomes of angioplasty and surgical bypass. ^[40] The researchers studied 70 elderly patients with atheromatous disease and found that angioplasty caused major complications, including two deaths. Kidney function improved (ie, > 20% decrease in serum creatinine level) in 57.5% of surgery patients but in only 15.8% of angioplasty patients. After 48 months of follow-up, the unassisted patency rate was only 69% in the angioplasty group compared with 100% in the surgical group.

Erdoes et al examined the results of 58 surgical and 18 percutaneous revascularizations in nonrandomized patients. ^[41] These two approaches showed similar operation risk (mortality rate 4.8-5.3%); however, functional improvement (ie, blood pressure, serum creatinine level) and patency of the renal artery were dramatically better in the surgical group than in the revascularization group after nearly 4 years of follow-up.

van Jaarsveld et al reported the results of a multicenter trial designed to evaluate the relative benefit of angioplasty versus medical therapy for hypertension associated with renovascular disease. ^[42] They found that both groups had similar decreases in blood pressure, although the patients who underwent angioplasty used one fewer hypertensive medication. While kidney function was improved at 3 months in those undergoing angioplasty, the function at 12 months was similar. They concluded that restricting angioplasty to those with atherosclerotic renovascular hypertension persisting despite use of three or more antihypertensive medications was prudent. Note that the patients in this trial did not undergo angioplasty with stent placement. In addition, 9% of patients in the medical therapy–only group demonstrated total occlusion of the affected renal artery on 12-month follow-up angiography.

A randomized study by van de Ven et al that compared percutaneous transluminal angioplasty (PTA) with PTA plus stenting (PTAS) for ostial atherosclerotic renal artery stenosis showed that PTAS is better than PTA for achieving vessel patency in these patients. ^[43] The primary success rate was 88% for PTAS compared with 57% for PTA. The restenosis rate after a successful primary procedure was 14% for PTAS versus 48% for PTA. In the last few years, the use of PTAS in patients with ostial stenosis or early restenosis has led to a considerable reduction in the restenosis rate.

However, controversy still surrounds the best approach to patients with atherosclerotic renovascular disease. ^{[44, 45, 46, 47]} A study  by Bax et al found that renal artery stenting had no clear effect on kidney function impairment in patients with atherosclerotic renal artery stenosis, and led to significant complications in some of them. ^[48] The multicenter trial included 140 patients with creatinine clearance of 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.

In the study, progression of kidney 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 (hazard ratio, 0.73 [95% confidence interval [CI], 0.33-1.61]). Serious complications in the stent group included two procedure-related deaths. ^[48]

The 2009 ASTRAL trial "found substantial risks but no evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease". ASTRAL included 806 patients with at least one stenotic renal artery and an estimated GFR of approximately 40 mL/min who were randomized to revascularization (ie, interventional radiology) or medical therapy. No difference was observed in the primary outcome, decline of kidney function, between the two groups. ^[49] Although the ASTRAL trial, like the study by Bax et al, had some design flaws, the results suggest that medical therapy is appropriate for patients with a single stenotic renal artery. Two review articles, one by Simon and another by Lao et al, discuss this subject in significant detail. ^{[50, 51]}

A multicenter review reported that the frequency of PTA for renal artery stenosis decreased in the years following the publication of the ASTRAL trial, indicating a higher threshold for invasive treatment of these patients. However, 4 years mean clinical follow-up suggested that most patients being treated with PTA benefited from the procedure, with reduced blood pressure, reduced need for anti-hypertensive medication, and stabilization of kidney function. ^[52]

The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study demonstrated no added benefit from the addition of stenting to medical therapy for renal artery stenosis. In CORAL, 947 participants with atherosclerotic renal-artery stenosis and either systolic hypertension or chronic kidney disease were randomized to medical therapy plus renal artery stenting or medical therapy alone. The resulting rate of adverse cardiovascular and renal events (ie, death, myocardial infarction, stroke, hospitalization for heart failure, progressive kidney insufficiency, or the need for renal replacement therapy) showed no significant differences (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% CI, 0.76 to 1.17; P = 0.58). ^[53]

However, a post hoc analysis of CORAL by Murphy et al found that in patients whose baseline urine albumin/creatinine ratio was at or below the median (22.5 mg/g), renal artery stenting was associated with significantly better outcome, including event-free survival, cardiovascular disease–related death, progressive kidney insufficiency, and overall survival. The authors suggest that low albuminuria may identify a potentially large subgroup of renal artery stenosis patients who would benefit from stent placement plus medical therapy. ^[54]

A meta-analysis of revascularization versus medical therapy for the treatment of renal artery stenosis found no clear benefit from percutaneous transluminal angioplasty with or without stenting over medical management. In the final analysis, which included 540 studies and seven randomized controlled trials and 2,139 patients, angioplasty with or without stenting was not superior to medical therapy with respect to any outcome. The incidence of nonfatal myocardial infarction was 6.74% in both the stenting and medical therapy group (odds ratio 0.998, 95% CI 0.698 to 1.427, P = 0.992), and the incidence of renal events with stenting population was 19.58% versus 20.53% with medical therapy (odds ratio 0.945, 95% CI 0.755 to 1.182, P = 0.620). ^[55]

Revascularization may not result in restoration of kidney function because of damage sustained during the period of reduced blood flow. ^[8] Hypoxia can result in functional loss of microcirculation (rarefaction) and recruitment of inflammatory cellular elements (as indicated by elevation of inflammatory biomarkers ^[56] ) that ultimately produce fibrosis. ^[45]

However, there is also evidence that percutaneous revascularization may benefit some patients in high-risk subgroups. In a retrospective analysis of a single-center prospective cohort study of 467 patients, Ritchie and colleagues reported that those individuals presenting with flash pulmonary edema, rapidly declining kidney function, or refractory hypertension who received revascularization had a significantly reduced risk for death and cardiovascular events compared with those who received medical management. ^[57]

In a single-center, case-control study that included 188 patients with renal artery stenosis, Meredith and colleagues identified previous myocardial infarction, left ventricular ejection fraction (LVEF) ≤35%, and GFR ≤45 mL/min/1.73 m² as risk factors. Renal artery stenting was associated with a 43% reduction in mortality in patients with none or one of those risk factors, but stenting had no effect on mortality in patients with two or three risk factors. ^[58]

Use of renal artery revascularization has been declining in recent years, mainly because trials to date have failed to demonstrate major advantages from the procedure. However, in a 2013 review, Textor et al note that trials of revascularization “have been small, conducted over short intervals, and have been ferociously criticized on methodologic grounds”. ^[59] These authors observe that endovascular repair is most likely to succeed when it is performed in patients with a recent deterioration in kidney function, which argues for careful identification and selection of patients for revascularization before loss of GFR becomes far advanced.

In some institutions, PTAS is the first-step approach in patients with ischemic renal disease, and practitioners reserve surgery for the technical failure of percutaneous maneuvers. However, surgery remains the first choice of treatment under certain conditions, including the following:

• Simultaneous abdominal aortic aneurysm
• Renal artery aneurysm
• Renal artery occlusion (with unsuccessful thrombolysis)
• Renal artery rupture
• Renal artery stenosis secondary to kinking
• Peripheral multifocal stenosis
• Unsuccessful angioplasty

A small, retrospective review of 20 patients older than 55 years with chronic kidney disease and proximal renal artery stenosis who underwent a revascularization procedure (ie, surgery, PTA, PTAS) revealed a high complication rate (increased serum creatinine concentration in 25%, eosinophilia in 5%, atheroemboli in 15%, renal artery dissection in 5%) and improved serum creatinine values in only 25%. ^[60] Fifty percent of patients had stable azotemia. The authors conclude that a prospective, randomized trial of medical management with or without PTAS is warranted for this complex clinical problem.

Renal artery fibromuscular dysplasia

PTA is the treatment of choice for renal artery fibromuscular dysplasia. A retrospective analysis by Yang et al of 76 PTA procedures in 64 patients reported that in the majority of cases (79.7%) the patient experienced immediate clinical benefit, with cure of hypertension in 35.9% and improvement in hypertension and a lower requirement for antihypertensive medications in 43.8%. In the long term (mean, 47.5 months), the survival rate was 96.9%, freedom from restenosis was 84.4%, and 76.6% of patients showed a sustained clinical benefit (cure rate 40.6%, improvement rate 35.9%). ^[61]

Patients with restenosis showed good response to repeat PTA. Eight patients were treated with a second procedure and two had a third procedure, resulting in improvement in hypertension in half of those patients. ^[61]

Kidney transplant recipients

In kidney transplant recipients, PTA and PTAS are the standard of care for renal artery stenosis. ^{[62, 63, 64]} However, good long-term outcomes with medical management have been reported in transplant recipients with less than 50% stenosis. ^[65] A comparison of PTA (n=34)  with PTAS (n=31) in kidney transplant recipients reported that freedom from graft failure or renal artery restenosis was significantly higher for PTAS at 1 year, but similar for PTA and PTAS at 10 years. ^[64]

The optimal approach to therapeutic interventions should be developed in consultation with an interventional radiologist and vascular surgeon. The relative expertise of these subspecialists at the individual medical center will determine the best course of action for the patient.

In view of the natural history of RVD, patients require serial determinations of serum creatinine levels. Adequate blood pressure control is required, with monitoring of serum potassium levels as necessary. Duplex ultrasound, if available, allows regular follow-up of radiologic progression.