Renal Fibromuscular Dysplasia: A Not So Common Entity of Secondary Hypertension

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1 REVIEW PAPER Renal Fibromuscular Dysplasia: A Not So Common Entity of Secondary Hypertension Elias A. Sanidas, MD, PhD; 1 Maria Seferou, MD; 1 Dimitris P. Papadopoulos, MD, FESC; 1 Anastasios Makris, MD; 1 Nora A.Viniou, MD, PhD; 1 Vasiliki Chantziara, MD, PhD; 1 Vasiliki Cennimata, MD; 1 Vasilios Papademetriou, MD 2 From the ESH Center of Excellence for Hypertension, Laiko General Hospital, Athens, Greece; 1 and Hypertension and Cardiovascular Research Clinic, Veterans Affairs and Georgetown University Medical Centers, Washington, DC, USA 2 Fibromuscular dysplasia is a rare noninflammatory vascular disease characterized by nonatheroslerotic stenosis predominantly seen in young women, whereas the majority of cases involve the renal arteries causing secondary hypertension. Most noninvasive screening tests are not quite sensitive or reproducible to rule out renal artery stenosis, but renal angiography usually confirms the diagnosis. Percutaneous renal artery angioplasty is the treatment of choice; however, it may not result in normalization of blood pressure if diagnosis is delayed. Continued follow-up is necessary since stenosis reoccurs. J Clin Hypertens (Greenwich). 2016;18: ª 2015 Wiley Periodicals, Inc. Of all patients with hypertension (HTN), more than 95% have benign (primary) HTN. Secondary causes of HTN can be identified in <5% of patients with HTN, but, unlike the former, secondary HTN is a potentially reversible medical condition. The list of secondary causes includes primary hyperaldosteronism, pheochromocytoma, thyroid disease, and renal parenchymal disease (6% 8%). Renovascular HTN, however, is among the most common causes of secondary HTN (3% 4%). 1 Renovascular disease is a common but still complex disorder that presents either as asymptomatic renal artery stenosis or renovascular HTN (RVH) or even as ischemic nephropathy and is mainly attributable to atherosclerosis. RVH is found among 1% to 5% of the hypertensive population or in 20% to 40% of patients with severe, refractory HTN or those undergoing diagnostic coronary arteriography. 2 In about 10% of patients with RVH, the narrowing of the lumen is caused not by atherosclerosis but by the entity known as fibromuscular dysplasia (FMD). These patients are usually young and predominantly female. 3 The result is profound angiotensin-mediated vasoconstriction and aldosterone-induced sodium and water retention, causing RVH. 4 The aim of this article is to review contemporary practices regarding the entity of FMD as one of the causes of RVH. DEMOGRAPHICS Definition FMD is currently defined as an idiopathic, segmental, noninflammatory, and nonatherosclerotic disease of the Address for correspondence: Dimitris P. Papadopoulos, MD, FESC, ESH Center of Excellence for Hypertension, Laiko General Hospital, 17 Agiou Thoma Str, 11527, Athens, Greece jimpapdoc@yahoo.com Manuscript received: May 9, 2015; revised: July 1, 2015; accepted: July 5, 2015 DOI: /jch musculature of arterial walls leading to stenosis, aneurysms, dissections, and occlusions of small- and medium-sized arteries, namely the renal and carotid arteries. Conversely, it is less common in the coronary, iliac, and abdominal visceral arteries. Historically, it was first described by Leadbetter and Burkland at John Hopkins Medical Center in 1938 in the renal artery of a young boy with severe uncontrolled HTN that was cured with nephrectomy. 3,5 Epidemiology The disease involves the renal arteries with a frequency of 60% to 75%. The right renal artery is the dominant site of FMD although a bilateral appearance is also possible in up to 40% of cases. Medial FMD is confined to the distal two thirds of the renal artery and involves the branch vessels in about 40% of patients. Progression of medial FMD occurs in almost one third of renal arteries. Total occlusion is rare. Renal artery aneurysms are not uncommon, but these rarely rupture. 6,7 In a recent registry from the United States it was found that among patients with renal artery FMD, coexistent extracranial carotid or vertebral artery disease was present in 65% of patients who underwent neuroimaging. Likewise, among patients with extracranial carotid or vertebral artery disease, coexistent renal FMD was present in 65% of patients who underwent renal imaging. 8 PATHOPHYSIOLOGY Causes The etiology of FMD is unknown, although various hormonal and mechanical factors have been suggested. Environmental factors such as smoking, exposure to endogenous or exogenous estrogens, and repeated stretching of the renal artery as in kidney mobility have also been associated with FMD, but the exact association remains unclear. Subclinical lesions are found at arterial sites distant from the stenotic arteries, and this 240 The Journal of Clinical Hypertension Vol 18 No 3 March 2016

2 suggests that FMD is a systemic arterial disease. It appears to be familial in 10% of cases, especially among Caucasians. In addition, an association between FMD and the HLA-DRw6 histocompatibility antigen has also been described. 5 A retrospective analysis of 104 patients with renal FMD showed a prevalence of 11% for familial cases, ie, 11% of cases had at least one sibling with angiographic evidence of renal artery FMD. 9 A number of studies have been conducted to define whether polymorphisms of angiotensin-converting enzyme (ACE) I/D, angiotensin II type 1 receptor (AT1R), and angiotensinogen play a role in the development of FMD. The only relationship found was that multifocal FMD patients had a significantly higher frequency of the ACE I allele than control patients. 10 CLASSIFICATION Histological Types Renal FMD represents a group of disorders characterized by fibrous or muscular hyperplasia in one or more layers (intima, media, and adventitia) of the renal artery wall. 11 These types have also been described in extrarenal arteries. 12 The most frequent form of renal FMD is medial fibromuscular disease, which occurs in approximately 65% to 70% of cases and has a classic string-ofbeads appearance at conventional angiography with or without aneurysm formation. Less common is the perimedial (subadventitial) form, which occurs in approximately 15% to 20% of cases and is angiographically characterized by aneurysm formation and focal or long stenosis. Isolated intimal and adventitial involvement is extremely rare (1% 2% of cases). 13 Of note, medial hyperplasia, which occurs in 8% to 10% of cases, has no pathognomonic radiological appearances. In the medial type of renal FMD, the lesion is a homogeneous collar of elastic tissue that presents as multiple stenoses interspersed with aneurysmal outpouchings, with a preserved internal elastic lamina. Perimedial renal FMD involves excessive tissue deposition at the junction of the media and adventitia. The three types are not mutually exclusive. Intimal FMD is characterized by irregularly arranged mesenchymal cells within a loose matrix of subendothelial connective tissue and a fragmented internal elastic lamina. 5 Angiographic Types Taking into consideration that pathological samples are rarely available, the diagnosis and classification of renal FMD has to be based on the angiographic appearance of stenoses. In this context, Kincaid and colleagues 14 proposed an angiographic classification of renal FMD into four types. The multifocal type, with multiple stenoses and the string-of-beads appearance; the tubular type, with a long concentric stenosis; the focal type, with solitary stenosis <1 cm in length; and the mixed-type. It appears that multifocal stenoses probably denote the presence of medial-type FMD. 14 Consequently, another study suggests that a binary angiographic classification into unifocal and multifocal types of FMD is clinically relevant. Unifocal and multifocal types of FMD have different nonangiographic phenotypes. Unlike histological classifications that can be applied only to operated patients, the angiographic classification can be used for all FMD patients. 15 CLINICAL MANIFESTATIONS The clinical presentation of FMD is primarily determined by the distribution of affected arteries. When the renal arteries are involved, the patient may present with HTN, whereas carotid artery involvement may lead to headache, pulsatile tinnitus, transient ischemic attack, or stroke. FMD might also be asymptomatic and discovered only incidentally when imaging is performed for a different clinical indication. 8 The most described clinical appearance of FMD is RVH secondary to renal artery involvement. Renal artery stenosis caused by FMD might be associated with all stages of HTN, but it is usually detected in patients with stage 2 or 3 HTN or abrupt onset of resistant HTN, since these are the individuals who undergo the most comprehensive etiological examinations. Upper abdominal quadrant or flank bruits are common in patients with renal artery FMD 9 but this clue has only limited diagnostic sensitivity and specificity. Patients with FMD are quite hypertensive but usually do not develop renal insufficiency. 2 Unlike atherosclerotic renal artery stenosis, FMD renal artery disease is rarely associated with high serum creatinine levels. 5 FMD may be complicated by renal artery dissection and kidney infarction with abrupt flank pain, hematuria, and rapidly progressive HTN. As a result of activation of the renin-angiotensin system, hypokalemia reflecting secondary hyperaldosteronism might be present, particularly in cases complicated with renal artery dissection and kidney infarction. 16 In the US registry for FMD, only 7.3% reported a confirmed diagnosis of FMD among family members. In contrast, there was a high prevalence of stroke (53.5%), aneurysm (23.5%), and sudden death (19.8%) 8 among family members. In a substudy from the same database, the mean age at diagnosis was 51.9 years. HTN and headache were the most prevalent presenting symptoms, leading to the diagnosis of FMD in both sexes. Of interest, women were more likely to present with extracranial carotid/vertebral artery stenosis than men, with a higher rate of pulsatile tinnitus. 17 Clinical manifestations of resistant HTN (and not only FMD) are seen in Table I. Physicians should look carefully for such signs once the suspicion of FMD has come into question. 18 The Journal of Clinical Hypertension Vol 18 No 3 March

3 TABLE I. Clinical Signs Suggestive of Renovascular Disease Abrupt onset of hypertension (HTN) before age 30 or after age 55 Accelerated, malignant, or severe HTN HTN refractory to multiple drug treatment Moderate to severe HTN in the presence of diffuse atherosclerosis Presence of systolic/diastolic epigastric bruit Moderate to severe HTN with unexplained renal insufficiency Significant azotemia induced by an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker Asymmetry of kidney size Unexplained flash pulmonary edema in patients with HTN DIAGNOSIS Diagnosis of FMD is not simple. To begin with, the clinical index of suspicion remains paramount in developing an appropriate diagnostic strategy. Differential diagnosis includes other causes of secondary HTN and atherosclerotic renal artery stenosis since they share common clinical presentations. 2 The results from the US registry showed a median time of years between the onset of symptoms and diagnosis of FMD. Contributing factors for this delay were presenting with HTN and taking multiple antihypertensive medications before diagnosis. However, patients presenting with arterial dissections have a shorter time interval between presenting symptoms and diagnosis of FMD and were more likely to have a timely diagnosis. The aforementioned observation raises the concern for delay in evaluation of FMD as a secondary cause of HTN. 19 Functional Tests Common functional tests for the diagnosis of renovascular disease include plasma renin activity (PRA), captopril plasma renin activity, renal vein renin sampling, and ACE inhibitor augmented scintigraphy. A suppressed PRA (<1) makes uncomplicated RVH less likely, while extremely high values (>10) suggest that a more careful workup be performed. The captopril plasma renin test has high sensitivity but, like PRA, low specificity. Renal vein renin sampling is invasive, inconvenient, and difficult to perform, yet it can be particularly helpful in determining the functional significance of a renal artery lesion with borderline angiographic appearance. ACE inhibitor augmented scintigraphy is based on the decrease in glomerular filtration rate and renal blood flow of the ischemic kidney in the setting of ACE inhibition. As mentioned above, FMD does not typically cause ischemic nephropathy; therefore, it is not suitable for patients with high clinical index for FMD. Furthermore, functional tests are limited by the need to discontinue medications that affect the renin-angiotensin system and their decreased accuracy in the setting of bilateral disease or renal insufficiency. 2 Imaging The limitations of functional tests along with the fact that they cannot differentiate between FMD and atherosclerotic stenosis makes the use of imaging techniques necessary. Imaging tests look for the anatomic presence of renal artery stenosis, not functional or clinical significance. They maintain their accuracy in renal insufficiency but they are more accurate in the presence of proximal main stenosis and decrease in distal accessory stenosis, more common in FMD. The most widespread modalities used are duplex ultrasound, computed tomography angiography (CTA), and magnetic resonance angiography (MRA). Nevertheless, conventional contrast angiography remains the gold standard in confirming the diagnosis. 2 The least expensive and easiest to handle diagnostic tool is color duplex ultrasound. However, the accuracy of this method depends on the skill of the operator and the quality of the duplex machine. Therefore, it is limited by not uniformly defined criteria for the detection of a hemodynamically relevant renal artery stenosis. 20 It is debatable whether MRA or CTA is better in diagnosing FMD. Both have high sensitivity and specificity but are both generally limited to patients with proximal main renal artery disease. 2 It has been shown that CT angiography gives good results in the depiction of FMD but exposes the patient to ionizing radiation and to potentially nephrotoxic iodinated contrast material. 13 Contrast-enhanced MRA with injection of gadolinium-based contrast material avoids these two hazards, but breath-holding, claustrophobia, and prosthetics are limitations. 2 The main limitation, however, of contrast-enhanced MRA for the diagnosis of renal FMD has been its lack of spatial resolution and its inability to demonstrate the distal portion and small intra-renal branches of the main renal artery. 21 Recent improvements in MRA imaging and contrast-enhanced MRA, which increase spatial and temporal resolution without diminishing the signal-to-noise ratio, promise that contrast-enhanced MRA can reliably facilitate diagnosis in patients with renal FMD by demonstrating characteristic lesions. 22 Conventional angiography is currently used to determine the location and the extent of renal artery involvement. 22 A diagnostic aortogram is part of the initial diagnostic workup, but this alone does not provide adequate evaluation of the renal arteries. Selective renal angiography is essential and often multiple views are required to fully profile the renal arteries and define the branch and intrarenal arterial anatomy. 23 Focal stenoses, the string-of-beads appearance (indicating multiple stenoses), and aneurysm are classic arteriographic signs of FMD (Figure). 7 In most cases, these findings coexist in various combinations, and in elderly patients these classic signs may coexist with atherosclerotic disease. 13 A stenosis was defined as a narrowing of 50% or more in diameter of the renal artery; an aneurysm was defined as an abnormal widening of the 242 The Journal of Clinical Hypertension Vol 18 No 3 March 2016

4 artery, with loss of parallelism of the vascular wall of the artery; and a string-of-pearls appearance was defined as a sequence of outpouchings along the course of the renal artery, simulating beads threaded onto a string. 7 Contrast angiography or digital subtraction angiography demonstrates excellent resolution, high accuracy, and ability to simultaneously measure a pressure gradient across the lesion; on the other hand, it is invasive and expensive and has low but significant risk of complications (pseudoaneurysm, hematoma, contrastinduced nephropathy, renal artery or aortic dissection, cholesterol embolization). Moreover, it detects the stenosis but not the functional significance of a lesion. 2 Since bilateral stenosis might occur in more than 33% of patients, meticulous evaluation of both kidneys and their intrarenal branches is requisite. 23 In a study comparing contrast-enhanced MRA with digital subtraction angiography, overall agreement between in the diagnosis of FMD was nearly perfect (j=0.91). The major finding in this study was that contrast-enhanced MRA can be used to detect renal artery FMD with a sensitivity of 97% (95% confidence interval, 83% 100%). Contrast-enhanced MRA was better for the diagnosis of the string-of-beads appearance than for the diagnosis of stenosis, with sensitivities of 95% (95% confidence interval, 74% 100%) and 68% (95% confidence interval, 41% 85%), respectively. 22 A recent advancement contributing to the accuracy of the diagnosis of FMD is the use of intravascular ultrasound (IVUS). IVUS gives a detailed understanding of the severity of the stenosis and assists in accurate sizing of balloons. In addition, utilizing IVUS to evaluate restenosis after endovascular therapy for FMD can be extremely valuable. 24 Finally, from a physiological point of view, measuring pressure gradients with a catheter or pressure wire is a diagnostic approach that remains controversial because the webs associated with FMD can be compressed and this may cause a false-negative reading. Additionally, there could be a flow-mediated impact on downstream tissue that is independent of the gradient. 24 function, which is usually reversible after the discontinuation of the drugs. In one study, 188 patients with RVH were treated for up to 3 months with ACE inhibitor based therapy. Complete control of BP was achieved in 74% of patients, partial control in 8% of patients, and no improvement in only 5% of patients. Captopril was discontinued secondary to side effects in only 13% of patients. 2 However, it has to be considered that medical therapy has limitations in the treatment of HTN in patients with renal artery stenosis. These include limited patient compliance in taking the prescribed drugs with resultant inadequate BP control. ACE inhibitors, diuretics, and other antihypertensive drugs may lead to acute ischemic nephropathy in patients with renal artery stenosis. Furthermore, under medical treatment alone, progressive development of chronic ischemic nephropathy has been described. 20 Lastly, even though there is no recommended surgical treatment for asymptomatic FMD, patients should be given antiplatelet therapy and statins if not contraindicated. 3 Nevertheless, the nature of progression of the disease along with minimal effects on renal function have suggested pharmacotherapy medical treatment only as the initial step for patients with FMD. Interventional Therapy In general, revascularization is recommended for patients with hemodynamically significant renal artery stenosis (Figure 1 and Figure 2), ie, with bilateral stenosis or unilateral stenosis causing more than 60% reduction in luminal diameter, and accelerated HTN, MANAGEMENT The goals of treatment for FMD include: (1) control of blood pressure (BP), (2) preservation of renal function, and (3) avoidance of complications and adverse effects of treatment. Management choices include medical management, percutaneous interventions (angioplasty- PTA and stenting), and surgical revascularization. Medical Treatment Proper medical management is an aggressive pharmacologic approach. It can be implemented either as a sole treatment modality or as an adjunct to percutaneous or surgical interventions. ACE inhibitors and ARBs are used effectively for BP control but there is a risk of acute decline of renal FIGURE 1. Baseline preintervention angiography of the right renal artery showing the typical string-of-beads morphology illusive for the diagnosis of fibromuscular dysplasia. The Journal of Clinical Hypertension Vol 18 No 3 March

5 TABLE II. Negative Prognostic Factors of Invasive Therapy (Percutaneous Transluminal Angioplasty or Stenting) Kidney size <8 cm Serum creatinine >3 4 mg/dl Another potential cause for renal dysfunction (eg, diabetes, amyloidosis) Long-standing essential hypertension Bilateral renal artery stenosis Decreased left ventricular function Long-standing renal dysfunction Extensive burden of atherosclerosis FIGURE 2. Postintervention angiography of the right renal artery without the typical string-of-beads morphology of fibromuscular dysplasia. PCI indicates percutaneous coronary intervention. resistant HTN, malignant HTN, HTN with an unexplained unilateral small kidney, and HTN intolerant to medication. 25 Older studies have demonstrated that revascularization of renal artery stenosis has numerous limitations. In these studies, HTN as the primary outcome was classified as cured, improved, or unchanged. However, the ability for direct comparison of these results seems limited because of significant differences in medical therapy, target BP, and technique of BP measurement. 26 Conventional balloon angioplasty is the therapy of choice for renal artery stenosis caused by FMD with cured or improved HTN in 60% to 90% of cases. 20 Recently published data suggest that cure of HTN reaches approximately 50%, with younger patients more likely to achieve this outcome. 27 Cutting balloons have proved to be effective in the setting of stenotic lesions of FMD that are resistant to conventional balloon angioplasty alone, particularly in stenoses related to intimal fibrodysplasia. These types of balloons have longitudinal blades that cut the vessel wall while reducing elastic recoil, improving the technical result and possibly long-term patency. Stenting is reserved exclusively for treating a complication of PTA, such as a dissection or rupture that cannot otherwise be fixed with a balloon. 23 In FMD, percutaneous intervention rather than medical therapy alone is generally considered the most advantageous intervention since it offers the possibility to cure HTN. FMD usually shows favorable clinical and anatomical response to PTA. Technical success is nearly 100% in most series. Clinically, there is a cure rate in the order of 40% to 50% with an additional 40% to 50% considered improved at last follow-up. Based on these results and the relatively low risk of complications, PTA is generally considered the initial procedure of choice for patients with RVH caused by FMD but may not result in normalization of BP if diagnosis is delayed. Furthermore, since restenosis occurs, continued follow-up is necessary (Table II). 2 Of interest, large series of patients failed to prove a beneficial effect on survival after revascularization despite the fact that ischemic nephropathy is an important cause of end-stage disease in those patients. Multivariate analysis found left ventricular cardiac dysfunction, age, and a baseline creatinine level >2.5 mg/dl to be independent predictors of mortality Potential complications of percutaneous interventions from the puncture site are hematoma and pseudoaneurysm; dissection, thrombosis, and bleeding from the renal artery; and systemic complications such as atheroembolism, myocardial infarction, acute renal failure, and infection. Risk factors for complications are considered extensive aortic atherosclerosis, significant cardiovascular disease, chronic renal failure, and increased age. 2 In contrast with FMD, atherosclerotic renal artery stenosis (ARAS) is usually segmental, typically involving the ostium and/or proximal one third of the renal artery and often the adjacent aorta. Although revascularization is not indicated in all patients with ARAS, it should be considered in those with hemodynamically significant stenosis and documented renal ischemia with viable underlying renal function or in those with difficult-tocontrol HTN. Several studies on renal artery intervention are summarized in Table III, seven of which included only patients with ARAS and three of which included patients with FMD Observational studies in ARAS have shown net clinical benefit with interventional therapy in terms of BP control and renal function preservation. Conversely, 244 The Journal of Clinical Hypertension Vol 18 No 3 March 2016

6 TABLE III. Major Interventional Studies for ARAS and FMD Study Year Patients Type Follow-Up Objective Results ARAS studies Dorros et al Prospective 4 years To evaluate PTA/stenting in ARAS Benefit van Jaarsveld et al RCT 1 year To compare PTA vs medical treatment in ARAS No benefit Dorros et al Prospective 4 years To evaluate PTA/stenting in ARAS Benefit Zeller et al Prospective 5 years To evaluate PTA/stenting in ARAS Benefit Zeller et al Prospective 6 years To evaluate PTA/stenting in ARAS Benefit Wheatley et al RCT 5 years To compare medical treatment vs medical No benefit treatment plus PTA/stenting in ARAS Bax et al RCT 2 years To evaluate PTA/stenting in ARAS No benefit FMD studies Mousa et al Retrospective 1 year To evaluate PTA/stenting in renal FMD Benefit Gavalas et al Prospective 2 5 years To evaluate PTA in renal FMD Benefit Fujihara et al Retrospective 6 years To evaluate PTA in renal FMD Benefit Abbreviations: ARAS, atherosclerotic renal artery stenosis; FMD, fibromuscular dysplasia; PTA, percutaneous transluminal angioplasty; RCT, randomized controlled trial. in randomized controlled trials, medical therapy indicated a similar effect in lowering BP compared with interventional therapy It is worth mentioning that neither type of study included patients with severe renal impairment To date there are no randomized controlled trials comparing interventional with medical management in patients with FMD. The only data available are derived from observational studies showing clinical benefit with interventional therapy. Periprocedural adverse effects that often complicate interventions in ARAS are rare in FMD, thus making patients with FMD more eligible for intervention In cases where FMD involves distal or smaller branches, percutaneous intervention becomes difficult and restenosis is more common. 23 Surgical procedures include endarterectomy, aortorenal bypass, and extra-anatomic bypass from the celiac or mesenteric branches. Even though there are no studies comparing endarterectomy with percutaneous interventions, and given that FMD is not focal but diffuse and sometimes bilateral, it seems that endarterectomy is not the first-line therapy for these patients. Furthermore, since percutaneous interventions are quite effective not only in BP control but also in preserving renal function, endarterectomy should be reserved solely for patients who cannot be treated otherwise. 23,27,35 37 Surgical bypass is primarily considered in the setting of macroaneurysms in which covered stents cannot be employed, in resistant intimal fibroplastic lesions, or in complex lesions where endovascular therapy cannot be used or has failed. Mortality ranges from 1% to 6%. Other complications are bleeding, infection, myocardial infarction, stroke, atheroembolic disease, and acute renal failure. Patients demonstrate excellent short- and long-term patency (85% 95% at 5 years), clinical improvement in HTN, and preservation of renal function. Surgical procedures are usually reserved for patients with concomitant aortic aneurysms requiring repair or complex lesions not amenable to percutaneous interventions. 2,23 CONCLUSIONS Fibromuscular dysplasia, although rare, is one of the curable causes of secondary HTN. It affects mostly young women, and percutaneous renal artery revascularization is currently considered the optimal treatment option with good outcomes in the majority of cases. Continued follow-up is mandatory if restenosis occurs or HTN is not adequately controlled. Disclosures: None. References 1. Chiong JR, Aronow WS, Khan IA, et al. Secondary hypertension: current diagnosis and treatment. Int J Cardiol. 2008;124: Bloch MJ, Basile J. Clinical insights into the diagnosis and management of renovascular disease. An evidence-based review. Minerva Med. 2004;95: Olin JW, Gornik HL, Bacharach JM, et al. 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J Vasc Surg. 2012;55: Gavalas MV, Gasparis AP, Tassiopoulos AK, et al. Long-term followup for percutaneous transluminal angioplasty in renal artery fibromuscular dysplasia. Int Angiol 2014 May 13. [Epub ahead of print]. 37. Fujihara M, Fukata M, Higashimori A, et al. Short- and mid-term results of balloon angioplasty for renal artery fibromuscular dysplasia. Cardiovasc Interv Ther. 2014;29: The Journal of Clinical Hypertension Vol 18 No 3 March 2016