Approach

The majority of patients with RAS have refractory or difficult-to-control hypertension, regardless of the etiology (fibromuscular dysplasia [FMD] versus atherosclerotic). Many patients may already be taking multiple antihypertensive medications.

The addition of aspirin and high-intensity statins should follow as part of secondary prevention measures. Control of other risk factors (such as tobacco cessation or glycemic control) is also recommended.

The role of percutaneous intervention remains controversial. It may be considered in patients with difficult-to-control hypertension despite aggressive medical therapy, in the presence of test results confirmatory of RAS. Other indications include a rapidly declining level of kidney function or recurrent flash pulmonary edema. Patient factors that may suggest clinical benefit of revascularization include a recent onset or exacerbation of hypertension (<1 year), absence of proteinuria, and identifiable activation of the renin-angiotensin system (e.g., hyperreninemia).

Surgical intervention is generally reserved for patients with concomitant vascular disease (e.g., abdominal aortic aneurysm [AAA]).

Only BP control with medications, with or without intervention, will prevent or limit end-organ damage, such as progression of chronic kidney disease, and palliate some of the manifestations of this disease, such as refractory pulmonary edema and angina. Patients with atherosclerotic RAS usually have concomitant cardiovascular disease, which should be aggressively treated.

Lifestyle modification recommendations for all patients

Low-salt diet:

  • May help improve BP in some patients.

Weight reduction:

  • May help improve BP in some patients.

Smoking cessation:

  • This is an important part of management in both atherosclerotic and FMD RAS patients.[14][16]

Optimization of glycemic control:

  • Tight glucose control with goal HbA1c <7% is known to decrease the risk of microvascular complications.[36] However, tight glycemic control has not been shown to decrease risk of macrovascular complications, and very tight control (HbA1c <6% to 6.5%) may worsen it.[37][38] Of antihyperglycemic agents, only metformin has been associated with possible reduced macrovascular risk.[36]

Outline of antihypertensive medications

Renin-angiotensin blockade with an ACE inhibitor or angiotensin II receptor antagonist is an attractive first-line antihypertensive strategy, as the actions target the mechanism of hypertension in RAS. Hypertension is a consequence of angiotensin II-related increase of systemic vascular resistance and stimulation of sodium retention, and ACE inhibitors have the potential to correct this state. However, some patients may not tolerate renin-angiotensin blockade, since GFR preservation may be dependent on high angiotensin II effect at the efferent arteriole to maintain intraglomerular pressure. It is recommended that BP, kidney function, and electrolytes be followed closely after initiating therapy.

First-line antihypertensives include captopril, enalapril, and angiotensin II receptor antagonists. The latter have not been studied in this population, but are generally considered equivalent to ACE inhibitors.[39][40][41][42] Second-line preferences include thiazide or loop diuretics,[41] beta-blockers,[42][43] calcium-channel blockers,[41][44] or prazosin.[41] Third-line choices include clonidine,[41] hydralazine, methyldopa,[43] or minoxidil. Methyldopa and minoxidil are generally reserved for patients unresponsive to all other therapies. Patients may require referral to a hypertension specialist (i.e., cardiologist or nephrologist).

Medical therapy versus intervention for atherosclerotic RAS

There is evidence that percutaneous vascular intervention plus medical therapy is no better than aggressive medical therapy alone.[45] Evidence from the largest randomized RAS clinical trial to date (CORAL trial, n=947) suggests that percutaneous vascular intervention with stenting did not confer a significant benefit with respect to the prevention of clinical events when added to a comprehensive aggressive and multifactorial medical therapy regimen in people with atherosclerotic RAS. Clinical events in this trial were a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy. There were no specific subgroups with potential benefit.[46]

Therefore, renal artery percutaneous vascular intervention should be reserved for selected cases after careful assessment by a vascular and endovascular specialist.

Atherosclerotic RAS first-line treatment: antihypertensive + lifestyle modification + statin + aspirin

Antihypertensives

Statin:

  • As atherosclerotic RAS is a type of vascular disease, statins should be considered for all patients. Although direct evidence is lacking for this recommendation, the high prevalence of concomitant peripheral vascular disease (PVD) and coronary artery disease (CAD) makes this recommendation reasonable. However, there are no published studies evaluating particular statin drugs, doses, or LDL cholesterol targets in this population. Weak evidence suggests that statins may slow the progression of atherosclerotic RAS.[47][48]

  • Any statin may be used, with a target LDL cholesterol <70 to 100 mg/dL.

  • Baseline and periodic evaluation of LFTs are recommended.

Antiplatelet therapy:

  • Aspirin should be considered for all patients with atherosclerotic RAS, because of the high likelihood of systemic cardiovascular disease.[16]

Atherosclerotic RAS second-line treatment: renal artery stenting

There are no data supporting renal artery stenting in asymptomatic patients in whom RAS is incidentally found.[2]

Current randomized data do not support routine percutaneous vascular intervention (angioplasty with or without stent deployment) in patients with atherosclerotic RAS.[45] Percutaneous intervention was no better than medical therapy in decreasing clinical events such as death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy in the CORAL trial, with similar findings reported in other studies.[45][46] Therefore, renal artery revascularization should be considered only in selected individuals after careful evaluation by a vascular/endovascular specialist.

Guidelines suggest renal artery stenting could be considered in the following circumstances in selected individual patients, as discussed above:[3][19][45][Figure caption and citation for the preceding image starts]: Digital subtraction angiography in a patient with significant atherosclerotic left renal artery stenosis. Panel A, prior to stent placement. Panel B, after successful stent deployment. Arrows indicate the site of stenosis and stent placement in their respective panelsCourtesy of Alvaro Alonso, MD and Scott J. Gilbert, MD [Citation ends].com.bmj.content.model.Caption@64ceb68b

  • Recurrent flash pulmonary edema

  • Stenosis of renal artery supplying single functioning kidney

  • Refractory hypertension on a multidrug regimen (>3 medications)

  • Patients with RAS, uncontrolled hypertension, and unstable angina

  • Acute kidney injury on ACE inhibitors/angiotensin II receptor antagonist in patients with CHF.

Patient factors that may suggest clinical benefit of revascularization include a recent onset or exacerbation of hypertension (<1 year), absence of proteinuria, and identifiable activation of the renin-angiotensin system (e.g., hyperreninemia).

One Japanese study found that renal percutaneous transluminal angioplasty was associated with a notable improvement in hypertension in those with atherosclerotic RAS.[49] Systolic blood pressure decreased by 10±9 mmHg following revascularization, accompanied by an increase in heart rate of 4±11 bpm.[49]

Patients should be referred to an endovascular interventions specialist if percutaneous vascular intervention is considered. Current medical therapy should be continued and maximized. Transient addition of clopidogrel should be considered for dual antiplatelet therapy after the procedure.

Atherosclerotic RAS third-line treatment: surgery

Surgical reconstruction of the renal arteries in the setting of RAS is restricted to those patients undergoing major aortic reconstruction for another reason, such as AAA repair or correction of severe aorto-iliac occlusive disease.[16] Medical therapy should be continued with regular monitoring. Surgery is associated with 1% to 6% mortality.

Fibromuscular dysplasia first-line treatment: antihypertensives + lifestyle modification + percutaneous renal artery balloon angioplasty

Antihypertensives

Percutaneous renal artery balloon angioplasty:

  • In addition to lifestyle modification and antihypertensive therapy, percutaneous renal artery balloon angioplasty should be considered first-line therapy, as it is often curative. Angioplasty has an initial technical success rate and 10-year patency rate of approximately 90%.[50]

  • The prospective DYSART study found that invasive trans-stenotic pressure measurement using a 4F catheter and guidewire was a more reliable indicator of procedural success in those with fibromuscular dysplasia compared to imaging assessment.[51]

  • One Japanese study found that renal percutaneous transluminal angioplasty was associated with a notable improvement in hypertension in those with fibromuscular dysplasia.[49] Systolic blood pressure decreased by 19±14 mmHg following revascularization, accompanied by an increase in heart rate of 2±4 bpm.[49]

Stenting:

  • Is not indicated for initial treatment except in cases of procedural complications during percutaneous renal artery balloon angioplasty (i.e., renal artery dissection). It could be considered in the setting of restenosis.[16]

  • Patients undergoing renal artery stenting require dual antiplatelet therapy (aspirin and clopidogrel) after the procedure.

Fibromuscular dysplasia second-line treatment: surgery

Surgical reconstruction of the renal arteries in the setting of FMD is restricted to those patients undergoing major aortic reconstruction for another reason. Surgical intervention may be necessary in complex disease that extends into the segmental arteries, and in cases of macroaneurysms.[16]

Medical therapy should be continued with regular monitoring.

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