Peripheral Vascular Disease

Renal Artery Fibromuscular Dysplasia

Katharine Rainer, BA, Chandan Devireddy, MD, Bryan J. Wells, MD,

Division of Cardiology, Emory School of Medicine, Emory University,

Atlanta, Georgia

Katharine Rainer, BA, Chandan Devireddy, MD, Bryan J. Wells, MD,

Division of Cardiology, Emory School of Medicine, Emory University,

Atlanta, Georgia

Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory arterial disease that primarily affects women.1 It most commonly affects the renal, extra-cranial carotid, and vertebral arteries, but has been reported in almost every arterial bed. FMD may cause stenosis, aneurysm, dissection and/or occlusion in affected vascular bed(s). Asymptomatic patients with FMD may be asymptomatic and have disease discovered incidentally during imaging for other reasons.2 Treatment consists of lifestyle modification, antiplatelet and antihypertensive therapy, and percutaneous or surgical revascularization and/or repair when indicated.3

Etiology

While many physicians consider FMD to be rare, it may not be that uncommon, but rather, under-recognized.4

Data from potential renal donors suggest it affects up to 4% of adult women.5 The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study reported a 5.8% prevalence of renal FMD in an older, more hypertensive and atherosclerotic patient population, compared with a 2.3% prevalence of renal FMD in a younger, healthier, renal donor population.6 Renal artery involvement occurs in 60-75% of patients with FMD, with bilateral involvement in 35%.7 Extra-cranial carotid artery involvement is approximately 75%.1 The cause of FMD is unknown, but hormonal, genetic and environmental factors have been considered.8 Autosomal dominant inheritance has been suggested in some families.9 However, registries report only a minority of FMD patients with a confirmed affected family member10, suggesting variable penetrance.11

Higher rates of bilateral and multivessel involvement have been observed in familial cases, which imply inherited disease may be more severe.12 Polymorphisms of the renin-angiotensin system have been studied in the pathogenesis of hypertension and atherosclerosis, which thus may also play a role in the development of FMD.13 A common variant located on chromosome 6 in the phosphatase and actin regulator gene (PHACTR1) was found to increase the risk of FMD by 40%.14 Hormonal factors such as estrogen have been proposed given the sex and age distribution of FMD.15 Lastly, history of smoking was strongly associated with FMD presenting with hypertension in younger patients.16

Classifications of FMD

FMD classification, which was once histological, is now based on two distinct angiographic appearances (Figure 1). A binary angiographic classification of focal (1) and multifocal (2) distinguishes two groups of patients with different clinical manifestations.17 Focal FMD, previously called intimal FMD, is less common and occurs in any part of the artery. Multifocal FMD, previously called medial FMD, with the characteristic “string of beads” angiographic pattern of stenosis and dilation, occurs in the mid and distal portions of the artery.3 Focal and multifocal FMD both commonly occur in the renal and carotid arteries.18 Classification studies demonstrate that multifocal is the more frequent phenotype.17 The median age of hypertension onset appears to be younger in those with focal FMD compared with multifocal FMD.19 Importantly, the presence of aneurysm, dissection or tortuosity without the presence of one focal or multifocal arterial lesions is not adequate to establish FMD diagnosis.18 Table 1 demonstrates the American Heart Association Classification based on angiographic and histologic categorizations.

Clinical Presentation

Clinical manifestations of FMD are variable and dependent on the vascular bed involved, as well as lesion severity. Among patients with FMD, 63% have more than one vascular bed affected. The most common manifestations of renal artery FMD are hypertension (63%), headache (52%), and pulsatile tinnitus (27.5%).3 Less commonly, flank pain due to renal artery dissection, aneurysm, or infarction may be initial presentation of renal artery FMD.3,5,20 Twenty to 40% of patients will have an aneurysm and/or dissection at the time of FMD diagnosis.21 The most severe presentations of FMD include transient ischemic attack, ischemic or hemorrhagic stroke, and myocardial infarction due to spontaneous coronary artery dissection.18 Table 2 outlines the clinical signs of renal artery FMD as established by the First International Consensus on the diagnosis and management of FMD.18

Diagnosis

Renal duplex ultrasound (Figure 2) of the renal arteries suggestive of FMD includes elevated velocities, turbulence of color or spectral Doppler flow, and tortuosity in the mid and distal segment of the renal artery and its branches.3 However, computed tomographic angiography (CTA) (Figure 1) is often used to reliably identify the classic “string of beads” characterization in patients with multifocal FMD, or the concentric or tubular stenosis in patients with focal FMD.22 Magnetic resonance angiography is used if CTA is contraindicated.18 Catheter-based angiography is the gold standard for diagnosis (Figure 3), but indicated only when the findings are expected to impact patient management, such as diagnostic uncertainty or planned intervention. In multi-focal renal artery FMD, imaging alone does not quantify the hemodynamic significance of renal artery stenosis. Translesional pressure gradient measurement with catheter-based angiography with the use of a flow wire is recommended to assess the hemodynamic significance of stenosis (Figure 3). The recommended protocol for catheter-based angiography in renal artery FMD is shown in Table 3.18

Treatment of FMD

The treatment for renal artery FMD is dependent on the presenting symptom (i.e., hypertension), lesion type (stenosis, aneurysm, dissection), and lesion severity (degree of stenosis). The U.S. Registry reported that 72.9% of patients are treated with antiplatelet therapy.23 Patients may present with thrombotic and thromboembolic events5, and therefore the use of antiplatelet therapy is appropriate. Given that hypertension is common among patients with FMD, the majority also receive antihypertensive medications.23 Smoking cessation is recommended as the U.S. Registry for FMD reports that patients with FMD with a history of smoking have higher rates of involvement than those who never smoked.24

For the treatment of renal and visceral artery dissection, medical therapy including antiplatelet or anticoagulation and surveillance imaging is appropriate.25 Interventional procedures including covered stent, coil embolization, or surgical repair are considered for progressive malperfusion, dissection, and/or pseudoaneurysm.18

In the case of renal artery aneurysm in patients without FMD, intervention is offered if the size is greater than 2 cm26 given the risk of distal embolization or rupture.27 However, in patients with FMD, there are limited data to determine the optimal frequency of surveillance and treatment. Renal artery aneurysms among patients with FMD can also be treated with endovascular intervention including covered stents (Figure 4), coiling, or surgery as is recommended in patients without FMD.27

For renal artery stenosis due to FMD, catheter-based angiography is necessary for measurement of a pressure gradient.18 A pressure gradient of 10% of mean aortic pressure is the suggested threshold for hemodynamically significant renal artery FMD appropriate for angioplasty, as has been extrapolated from atherosclerotic renal artery stenosis.28 A pressure gradient of close to zero should be achieved after balloon angioplasty is performed (Figure 3). The consensus protocol for catheter-based angiography and angioplasty in renal artery FMD is shown in Table 3.18 There is no added benefit for the use of stenting in angioplasty29 in renal artery FMD, and therefore it is only recommended for procedural complications18 such as dissection. In rare patients with complex FMD lesions, aneurysms, or failed angioplasty, surgical revascularization and repair is a possible approach to treatment.30

There are favorable outcomes after revascularization in renal FMD. In a meta-analysis across 11 studies, hypertension cure rate ranged from 14-85% after angioplasty, and 18% of patients required a repeat procedures.31 Focal FMD, younger patient age at the time of treatment, and shorter duration of hypertension are associated with a higher hypertension cure rate.17,31

Longitudinal care of symptomatic and asymptomatic FMD patients includes periodic monitoring of blood pressure and renal function, surveillance imaging (typically duplex ultrasound) of the affected vascular beds, and adherence to medical therapy.18

Further studies are needed to determine the etiology and natural history of FMD, in addition to improving its diagnosis and management. 

Three videos are available with the online version of this article at http://www.cathlabdigest.com.

Disclosures: The authors report no conflicts of interest regarding the content herein.

The authors can be contacted via Katharine Rainer, BA, at katharine.nian-hua.woo.rainer@emory.edu.

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